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      A review of brain circuitries involved in stuttering

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          Abstract

          Stuttering has been the subject of much research, nevertheless its etiology remains incompletely understood. This article presents a critical review of the literature on stuttering, with particular reference to the role of the basal ganglia (BG). Neuroimaging and lesion studies of developmental and acquired stuttering, as well as pharmacological and genetic studies are discussed. Evidence of structural and functional changes in the BG in those who stutter indicates that this motor speech disorder is due, at least in part, to abnormal BG cues for the initiation and termination of articulatory movements. Studies discussed provide evidence of a dysfunctional hyperdopaminergic state of the thalamocortical pathways underlying speech motor control in stuttering. Evidence that stuttering can improve, worsen or recur following deep brain stimulation for other indications is presented in order to emphasize the role of BG in stuttering. Further research is needed to fully elucidate the pathophysiology of this speech disorder, which is associated with significant social isolation.

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          Most cited references196

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          A forkhead-domain gene is mutated in a severe speech and language disorder.

          Individuals affected with developmental disorders of speech and language have substantial difficulty acquiring expressive and/or receptive language in the absence of any profound sensory or neurological impairment and despite adequate intelligence and opportunity. Although studies of twins consistently indicate that a significant genetic component is involved, most families segregating speech and language deficits show complex patterns of inheritance, and a gene that predisposes individuals to such disorders has not been identified. We have studied a unique three-generation pedigree, KE, in which a severe speech and language disorder is transmitted as an autosomal-dominant monogenic trait. Our previous work mapped the locus responsible, SPCH1, to a 5.6-cM interval of region 7q31 on chromosome 7 (ref. 5). We also identified an unrelated individual, CS, in whom speech and language impairment is associated with a chromosomal translocation involving the SPCH1 interval. Here we show that the gene FOXP2, which encodes a putative transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain, is directly disrupted by the translocation breakpoint in CS. In addition, we identify a point mutation in affected members of the KE family that alters an invariant amino-acid residue in the forkhead domain. Our findings suggest that FOXP2 is involved in the developmental process that culminates in speech and language.
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            The cerebellum is involved in predicting the sensory consequences of action.

            We used H2(15)O PET to examine neural responses to parametrically varied degrees of discrepancy between the predicted and actual sensory consequences of movement. Subjects used their right hand to move a robotic arm. The motion of this robotic arm determined the position of a second foam-tipped robotic arm, which made contact with the subject's left palm. Using this robotic interface, computer controlled delays were introduced between the movement of the right hand and the tactile stimulation on the left. Activity in the right lateral cerebellar cortex showed a positive correlation with delay. These results suggest the cerebellum is involved in signalling the sensory discrepancy between the predicted and actual sensory consequences of movements.
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              Lateralization of phonetic and pitch discrimination in speech processing.

              Cerebral activation was measured with positron emission tomography in ten human volunteers. The primary auditory cortex showed increased activity in response to noise bursts, whereas acoustically matched speech syllables activated secondary auditory cortices bilaterally. Instructions to make judgments about different attributes of the same speech signal resulted in activation of specific lateralized neural systems. Discrimination of phonetic structure led to increased activity in part of Broca's area of the left hemisphere, suggesting a role for articulatory recoding in phonetic perception. Processing changes in pitch produced activation of the right prefrontal cortex, consistent with the importance of right-hemisphere mechanisms in pitch perception.
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                Author and article information

                Contributors
                Journal
                Front Hum Neurosci
                Front Hum Neurosci
                Front. Hum. Neurosci.
                Frontiers in Human Neuroscience
                Frontiers Media S.A.
                1662-5161
                17 November 2014
                2014
                : 8
                : 884
                Affiliations
                [1] 1Imperial College School of Medicine London, UK
                [2] 2Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London London, UK
                [3] 3Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery London, UK
                Author notes

                Edited by: Angela T. Morgan, University of Melbourne, Australia

                Reviewed by: Alessandro Stefani, University of Rome, Italy; Béchir Jarraya, Institut National de la Santé et de la Recherche Médicale-Commissariat à l’Energie Atomique/ Versailles Saint-Quentin-en-Yvelines University-Hôpital Foch, France

                *Correspondence: Elina Tripoliti, Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK e-mail: e.tripoliti@ 123456ucl.ac.uk

                This article was submitted to the journal Frontiers in Human Neuroscience.

                Article
                10.3389/fnhum.2014.00884
                4233907
                25452719
                19849980-78c9-478e-9968-24ef37b3503d
                Copyright © 2014 Craig-McQuaide, Akram, Zrinzo and Tripoliti.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 June 2014
                : 14 October 2014
                Page count
                Figures: 2, Tables: 3, Equations: 0, References: 219, Pages: 20, Words: 0
                Categories
                Neuroscience
                Review Article

                Neurosciences
                stuttering,palilalia,speech neural control,basal ganglia,thalamus,deep brain stimulation
                Neurosciences
                stuttering, palilalia, speech neural control, basal ganglia, thalamus, deep brain stimulation

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