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Anatomy of the Respiratory Neural Network
Published in Susmita Chowdhuri, M Safwan Badr, James A Rowley, Control of Breathing during Sleep, 2022
Christopher A Del Negro, Christopher G Wilson
KF neurons can be distinguished from parabrachial neurons by FoxP2 expression. FoxP2 is associated with speech and vocalization. It is logical that an area with control of laryngeal muscles that regulates inspiration-expiratory phase transition, as well as post-inspiration, could be important for speech and vocalization. Further, in support of a KF role in speech and vocalization, the KF projects directly to the NTS, wherein a key subpopulation is essential for vocalization in mice (169). However, the relevance to human vocal control has not been established.
The Human Genome Project and Its Impact on Understanding Developmental Disabilities
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
Daniel J. Wattendorf, Maximilian Muenke
Comparative genomics has aided in the identification of the first gene involved in speech and language pathology, FOXP2, a member of the forkhead family of transcription factors. This gene was identified by the genetic analysis of a family and an unrelated boy with a chromosome rearrangement with both a specific speech deficit that impairs fine facial movements as well as a neural processing language deficit that interferes with the mental process of forming words (54). The ability to compare human sequence with DNA sequence from primates allowed the recognition that the specific sequence of the human variations of the FOXP2 gene were found at a frequency higher than expected by chance and fit with a model of natural selection. Thus, by finding sequence variations in patients with rare developmental disabilities and comparing these variations to sequences from model organisms, the genetic pathways defining human cognition may eventually be revealed.
Genetic contributions to neurodevelopmental disorders
Published in Anna L. Barnett, Elisabeth L. Hill, Understanding Motor Behaviour in Developmental Coordination Disorder, 2019
FOXP2 is an example of a “dosage sensitive gene”. The amount of FOXP2 protein is strictly regulated during development and genetic changes that alter its level appear to be particularly problematic. In mice, a complete lack of Foxp2 protein leads to motor impairment and premature death. Disruption of a single copy of the gene (as described in humans) results in developmental delay but is not lethal (Fujita et al., 2008; Shu et al., 2005). Thus FOXP2 is critical for survival and reduced levels lead to disorder. Does this mean that all changes in FOXP2 will result in verbal dyspraxia? DNA databases show that changes in FOXP2 occur less often than expected (Exome Aggregation Consortium, 2016) indicating that the gene sequence is highly constrained.
Human Brain Surrogates: Models or Distortions?
Published in The American Journal of Bioethics, 2021
Turning to the first point, consider an experiment in which mice were genetically engineered to carry a FOXP2 variant that causes language disorders in humans.1 Known as “the human language gene,” FOXP2 fell under the spotlight when it was identified as the cause of a severe speech and language disorder affecting about half the members (through four generations) of a large family in London. Researchers soon learned that the gene was highly conserved evolutionarily, which is to say that there are only three amino acid differences between the gene as found in humans and as found in mice. Despite that similarity, however, when the human variant was transferred to mice, the “humanized” mice did not exhibit apparent vocalization deficits. The disappointing outcome led to skepticism, with some researchers concluding that “[r]ecapitulation of specific human gene mutations does not … predictably recapitulate gene function in animal models” (Zhao and Bhattacharyya 2018, 832). In other words, the nonhuman body of the surrogate mouse—its genetics, development, and overall physiology—distorted the anticipated effects. The functional mechanisms used to produce human behavior were not replicated in the model even though they were thought to be the same mechanism.
The effect of dopamine on the comprehension of spectrally-shifted noise-vocoded speech: a pilot study
Published in International Journal of Audiology, 2020
Velia Cardin, Stuart Rosen, Linda Konieczny, Kim Coulson, Daniel Lametti, Mark Edwards, Bencie Woll
The neurotransmitter dopamine has a general role in assigning value to internal and external information (Schultz 2015), and it modulates learning in several domains, including audition, vocal function, and language. For example, dopamine improves sound discrimination learning in gerbils (Schicknick et al. 2008) and rats (Kudoh and Shibuki 2006). In addition, reducing dopaminergic input to the basal ganglia has been shown to impair vocal learning in songbirds (Hoffmann et al. 2016). In humans, L-DOPA, a precursor of dopamine, causes a moderate enhancement of word learning (Knecht et al. 2004; Shellshear et al. 2015), and influences semantic priming through modulation of prefrontal and temporal activity (Copland et al. 2009). Furthermore, increased activation in the ventral striatum, which receives strong dopaminergic inputs, has been observed when adults successfully learn the meaning of words (Ripollés et al. 2014). This is accompanied by enhanced functional connectivity between the ventral striatum and language areas during successful word learning (Ripollés et al. 2014). Moreover, the transcription factor FOXP2, associated with the acquisition of speech and language, has been shown to alter striatal function, including dopamine levels (Enard 2011).
Prenatal maternal depressive symptoms and infant DNA methylation: a longitudinal epigenome-wide study
Published in Nordic Journal of Psychiatry, 2019
Ellen Wikenius, Anne Margrethe Myhre, Christian Magnus Page, Vibeke Moe, Lars Smith, Einar Røshol Heiervang, Dag Erik Undlien, Marissa LeBlanc
T-box, brain 1 is a member of a family of genes that share the T-box as their common DNA-binding domain and is mainly expressed in brain tissue. TBR1 variants have been identified in sporadic autism, and in interaction with FOXP2 have been found to be involved in speech and language disorders [51]. Single nucleotide polymorphism (SNP) array analysis showed that de novo deletions in TBR1 were associated with intellectual disability and growth retardation [52]. In mice, prenatal maternal obesity has been associated with an increased number of Tbr1 in neurons in offspring that showed anxiety-like behavior as adults [53]