Contribution of the Cerebellum and the Basal Ganglia to Language Production: Speech, Word Fluency, and Sentence Construction—Evidence from Pathology

Silveri, Maria Caterina

doi:10.1007/s12311-020-01207-6

Cited by 63 publications

(27 citation statements)

References 161 publications

(192 reference statements)

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“…Only a subset of brain tissues available can be expected to yield gene expression estimates and so investigations should be limited to two or three “most relevant” brain regions for the phenotypes. In this case the cerebellum was identified by the FUSION workflow as having eQTL SNPs for NLGN4X , this region of the brain has also been identified as having a role in language (Price, 2012; Silveri, 2021). Therefore, investigating correlations between expression levels of NLGN4X in the cerebellum and language phenotypes had an underlying biological theory.…”

Section: Discussionmentioning

confidence: 99%

Analysis of expression Quantitative Trait Loci for NLGN4X in relation to language and neurodevelopmental function: an exploratory analysis using FUSION and GTEx workflows

Simpson

Bishop

Newbury

2021

Preprint

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Language disorders in children are highly heritable, but progress in identifying genetic variants that contribute to language phenotypes has been slow. Here we applied a novel approach by identifying SNPs that are associated with gene expression in the brain, taking as our focus a gene on the X chromosome, NLGN4X, which has been postulated to play a role in neurodevelopmental disorders affecting language and communication. We found no significant associations between expression quantitative trait loci (eQTLs) and phenotypes of nonword repetition, general language ability or neurodevelopmental disorder in two samples of twin children, who had been selected for a relatively high rate of language problems. We report here our experiences with two methods, FUSION and GTEx, for eQTL analysis. It is likely that our null result represents a true negative, but for the interest of others interested in using these methods, we note specific challenges encountered in applying this approach to our data: a) complications associated with studying a gene on the X chromosome; b) lack of agreement between expression estimates from FUSION and GTEx; c) software compatibility issues with different versions of the R programming language.

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Section: Discussionmentioning

confidence: 99%

Analysis of expression Quantitative Trait Loci for NLGN4X in relation to language and neurodevelopmental function: an exploratory analysis using FUSION and GTEx workflows

Simpson

Bishop

Newbury

2021

Preprint

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“…The most promising genes for explaining her language deficits are LIN7A (found strongly downregulated) and RAP1GAP (found strongly upregulated). Both genes are expressed in the brain, particularly in the cerebellum (LIN7A) and the striatum (RAP1GAP), which are two regions that are crucially involved in language processing (Silveri, 2020), particularly, in speech production (Konopka and Roberts, 2016). Deletions in LIN7A, a gene encoding a scaffold protein important for synaptic function, impact on the development of the cerebral cortex and result in ID (Matsumoto et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Delving into the genetic causes of language impairment in people with partial deletions of NRXN1

Benítez‐Burraco¹,

Jiménez-Romero²,

Fernández-Urquiza³

2022

Preprint

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Copy-number variations (CNVs) impacting on small DNA stretches and that are associated to language deficits provide a unique window to the role played by specific genes in language function. We report in detail on the cognitive and language features of a girl bearing a small deletion (0,186 Mb) in the 2p16.3 region (arr[hg19] 2p16.3(50761778-50947729)x1), affecting to exons 3-7 of NRXN1, a neurexin-coding gene previously related to schizophrenia (SZ), autism (ASD), attention deficit hyperactivity disorder (ADHD), mood disorder, and intellectual disability (ID). The proband exhibits many of the features commonly found in subjects with deletions of NRXN1, like ASD-like traits (including ritualized behaviors, disordered sensory aspects, social disturbances and impaired theory of mind), ADHD symptoms, moderate ID, and impaired speech and language. Regarding this latter aspect, we observed altered speech production, underdeveloped phonological awareness, minimal syntax, serious shortage of active vocabulary, impaired receptive language, and inappropriate pragmatic behavior (including lack of metapragmatic awareness and communicative use of gaze). Although these problems might arise from some basic cognitive deficit, such as the impairment of executive function, we provide evidence that several genes important for language function are dysregulated in the proband compared to their healthy parents.

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“…Second, the classic actor-critic model of the basal ganglia is an on-policy RL algorithm-it is designed to learn online from experiences driven by the basal ganglia's policy. However, motor control in biological systems is distributed, with multiple brain regions including the motor cortex and cerebellum exerting influence on behavior independent of the basal ganglia [16,54,2,44,5]. We show that classic actor-critic models of the basal ganglia fail in this scenario and argue that the ability to learn from off-policy experience is essential to models of basal ganglia learning.…”

Section: Introductionmentioning

confidence: 95%

Action-modulated midbrain dopamine activity arises from distributed control policies

Lindsey¹,

Litwin-Kumar²

2022

Preprint

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Animal behavior is driven by multiple brain regions working in parallel with distinct control policies. We present a biologically plausible model of off-policy reinforcement learning in the basal ganglia, which enables learning in such an architecture. The model accounts for action-related modulation of dopamine activity that is not captured by previous models that implement on-policy algorithms.In particular, the model predicts that dopamine activity signals a combination of reward prediction error (as in classic models) and "action surprise," a measure of how unexpected an action is relative to the basal ganglia's current policy. In the presence of the action surprise term, the model implements an approximate form of Q-learning. On benchmark navigation and reaching tasks, we show empirically that this model is capable of learning from data driven completely or in part by other policies (e.g. from other brain regions). By contrast, models without the action surprise term suffer in the presence of additional policies, and are incapable of learning at all from behavior that is completely externally driven. The model provides a computational account for numerous experimental findings about dopamine activity that cannot be explained by classic models of reinforcement learning in the basal ganglia. These include differing levels of action surprise signals in dorsal and ventral striatum, decreasing amounts movement-modulated dopamine activity with practice, and representations of action initiation and kinematics in dopamine activity. It also provides further predictions that can be tested with recordings of striatal dopamine activity. 1

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Contribution of the Cerebellum and the Basal Ganglia to Language Production: Speech, Word Fluency, and Sentence Construction—Evidence from Pathology

Cited by 63 publications

References 161 publications

Analysis of expression Quantitative Trait Loci for NLGN4X in relation to language and neurodevelopmental function: an exploratory analysis using FUSION and GTEx workflows

Analysis of expression Quantitative Trait Loci for NLGN4X in relation to language and neurodevelopmental function: an exploratory analysis using FUSION and GTEx workflows

Delving into the genetic causes of language impairment in people with partial deletions of NRXN1

Action-modulated midbrain dopamine activity arises from distributed control policies

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