Dopamine drives left‐hemispheric lateralization of neural networks during human speech

Fuertinger, Stefan; Zinn, Joel; Sharan, Ashwini; Hamzei-Sichani, Farid; Simonyan, Kristina

doi:10.1002/cne.24375

Cited by 10 publications

(4 citation statements)

References 58 publications

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“…Recent evidence suggests that the speech circuit is lateralized to the language-dominant side and this may explain why the benefit of thalamic DBS was lateralized in most of our patients [37, 38]. This unilateral benefit of thalamic DBS has been reported in other vocal pathologies by our group [8] and others [39].…”

Section: Discussionsupporting

confidence: 53%

Unilateral Thalamic Deep Brain Stimulation for Voice Tremor

Avecillas-Chasín

Poologaindran

Morrison

et al. 2018

Stereotact Funct Neurosurg

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Background: Voice tremor (VT) is the involuntary and rhythmical phonatory instability of the voice. Recent findings suggest that unilateral deep brain stimulation of the ventral intermediate nucleus (Vim-DBS) can sometimes be effective for VT. In this exploratory analysis, we investigated the effect of Vim-DBS on VT and tested the hypothesis that unilateral thalamic stimulation is effective for patients with VT. Methods: Seven patients with VT and previously implanted bilateral Vim-DBS were enrolled in the study. Each patient was randomized and recorded performing sustained phonation during the following conditions: left thalamic stimulation, right thalamic stimulation, bilateral thalamic stimulation (Bil-ON), and no stimulation (Bil-OFF). Perceptual VT ratings and an acoustic analysis to find the rate of variation of the fundamental frequency measured by the standard deviation of the pitch (f0SD) were performed in a blinded manner. For the purposes of this study, a “dominant” side was defined as one with more than twice as much reduction in VT following Vim-DBS compared to the contralateral side. The Wilcoxon signed-rank test was performed to compare the effect of the dominant side stimulation in the reduction of VT scores and f0SD. The volume of activated tissue (VAT) of the dominant stimulation side was modelled against the degree of improvement in VT to correlate the significant stimulation cluster with thalamic anatomy. Finally, tractography analysis was performed to analyze the connectivity of the significant stimulation cluster. Results: Unilateral stimulation was beneficial in all 7 patients. Five patients clearly had a “dominant” side with either benefit only seen following stimulation of one side or more than twice as much benefit from one side compared to the other. Two patients had similar benefit with unilateral stimulation from either side. The Wilcoxon paired test showed significant differences between unilateral dominant and unilateral nondominant stimulation for VT scores (p = 0.04), between unilateral dominant and Bil-OFF (p = 0.04), and between Bil-ON and unilateral nondominant stimulation (p = 0.04). No significant differences were found between Bil-ON and unilateral dominant condition (p = 0.27), or between Bil-OFF and unilateral nondominant (p = 0.23). The dominant VAT showed that the significant voxels associated with the best VT control were located in the most ventral and medial part of the Vim nucleus and the ventralis caudalis anterior internus nucleus. The connectivity analysis showed significant connectivity with the cortical areas of the speech circuit. Conclusions: Unilateral dominant-side thalamic stimulation and bilateral thalamic stimulation were equally effective in reducing VT. Nondominant unilateral stimulation alone did not significantly improve VT.

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Section: Discussionsupporting

confidence: 53%

Unilateral Thalamic Deep Brain Stimulation for Voice Tremor

Avecillas-Chasín

Poologaindran

Morrison

et al. 2018

Stereotact Funct Neurosurg

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“…Our data also provide a framework for future morphometric analysis of astrocytes in the primate brain. For instance, since vocalization is known to be lateralized to the left hemisphere (Fuertinger et al, 2018;Vigneau et al, 2006), it may be important to further investigate if there is a lateralized morphological differences in astrocytes. Understanding more about the role of astrocytes in control of complex motor behaviors might provide additional information for cell-targeting for novel pharmacogenomic strategies to interfere with motor control disorders, such as speech fluency disorders.…”

Section: Discussionmentioning

confidence: 99%

Morphometric analysis of astrocytes in vocal production circuits of common marmoset (Callithrix jacchus)

Turk

SheikhBahaei

2021

J of Comparative Neurology

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Astrocytes, the star-shaped glial cells, are the most abundant non-neuronal cell population in the central nervous system. They play a key role in modulating activities of neural networks, including those involved in complex motor behaviors. Common marmosets (Callithrix jacchus), the most vocal non-human primate (NHP), have been usedto study the physiology of vocalization and social vocal production. However, the neural circuitry involved in vocal production is not fully understood. In addition, even less is known about the involvement of astrocytes in this circuit. To understand the role, that astrocytes may play in the complex behavior of vocalization, the initial step may be to study their structural properties in the cortical and subcortical regions that are known to be involved in vocalization. Here, in the common marmoset, we identify all astrocytic subtypes seen in other primate's brains, including intralaminar astrocytes. In addition, we reveal detailed structural characteristics of astrocytes and perform morphometric analysis of astrocytes residing in the cortex and midbrain regions that are associated with vocal production. We found that cortical astrocytes in these regions illustrate a higher level of complexity when compared to those in the midbrain. We hypothesize that this complexity that is expressed in cortical astrocytes may reflect their functions to meet the metabolic/structural needs of these regions.

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“…Psychiatric, communicative, and cognitive problems may be related to the underlying dysfunction of dopaminergic pathways comprising the mesolimbic system, as these are involved in mood and attention regulation, working memory, and associative learning [60,62]. In addition, since primary language areas receive dopaminergic projections from subcortical regions [63], dysfunction of these pathways may influence the regulation of language processing. Furthermore, dopamine also plays a role in the executive functions via the mesocortical pathway, which are necessary for the organization of speech in expressive language and proper modulation of attention, necessary for adequate auditory processing and language comprehension [64].…”

Section: Discussionmentioning

confidence: 99%

NR4A2 as a Novel Target Gene for Developmental and Epileptic Encephalopathy: A Systematic Review of Related Disorders and Therapeutic Strategies

Gabaldon-Albero,

Mayo,

Martinez

2024

IJMS

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The NR4A2 gene encodes an orphan transcription factor of the steroid–thyroid hormone–retinoid receptor superfamily. This review focuses on the clinical findings associated with the pathogenic variants so far reported, including three unreported cases. Also, its role in neurodegenerative diseases, such as Parkinson’s or Alzheimer’s disease, is examined, as well as a brief exploration on recent proposals to develop novel therapies for these neurological diseases based on small molecules that could modulate NR4A2 transcriptional activity. The main characteristic shared by all patients is mild to severe developmental delay/intellectual disability. Moderate to severe disorder of the expressive and receptive language is present in at least 42%, while neuro-psychiatric issues were reported in 53% of patients. Movement disorders, including dystonia, chorea or ataxia, are described in 37% patients, although probably underestimated because of its frequent onset in late adolescence–young adulthood. Finally, epilepsy was surprisingly present in 42% of patients, being drug-resistant in three of them. The age at onset varied widely, from five months to twenty-six years, as did the classification of epilepsy, which ranged from focal epilepsy to infantile spasms or Lennox–Gastaut syndrome. Accordingly, we propose that NR4A2 should be considered as a first-tier target gene for the genetic diagnosis of developmental and epileptic encephalopathy.

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Dopamine drives left‐hemispheric lateralization of neural networks during human speech

Cited by 10 publications

References 58 publications

Unilateral Thalamic Deep Brain Stimulation for Voice Tremor

Unilateral Thalamic Deep Brain Stimulation for Voice Tremor

Morphometric analysis of astrocytes in vocal production circuits of common marmoset (Callithrix jacchus)

NR4A2 as a Novel Target Gene for Developmental and Epileptic Encephalopathy: A Systematic Review of Related Disorders and Therapeutic Strategies

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