Article
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Using the structural equation modeling (SEM) method, the present study examined the role of large-scale neural interactions in developmental stuttering while 10 stuttering and nine non-stuttering subjects performed a covert picture-naming task. Results indicated that the connection patterns were significantly different between stuttering and non-stuttering speakers in both omnibus connection pattern and individual connection path coefficient. Specifically, stuttering speakers showed functional disconnection from the left inferior frontal gyrus to the left motor areas, and altered connectivity in the basal ganglia-thalamic-cortical circuit, and abnormal integration of supramodal information across the cerebellum and several frontal-parietal regions. These results indicate that the large-scale dysfunctional neural interactions may be involved in stuttering speakers' difficulties in planning, execution, and self-monitoring of speech motor sequence during word production.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... In the past few decades, numerous studies have provided evidence on impaired neural function in speech production among PWS [13][14][15][16][17][18][19][20][21][22]. An ALE meta-analysis on the distinct brain activation patterns of persistent developmental stuttering revealed a right lateralization, with overactivation in the motor areas and cerebellum and decreased activation in the auditory areas [23]. ...
... Previous neuroimaging research has provided solid evidence for these two theories. In a picture naming study [19], deactivation in the superior temporal gyrus (STG) was found among stutterers; thus, the connections between the bilateral posterior superior temporal gyrus (pSTG) and putamen and thalamus among stutterers were weaker than those among non-stutterers. ...
... Preibisch [16] Overt reading > viewing meaningless signs 16 16 13 3 de Nil [18] Repeating words > passive listening 15 15 19 15 Watkins [50] Production with fluency or auditory feedback 10 10 11 21 Chang [51] Speech production > non-speech production 20 20 27 59 Kell [47] Overt > covert reading 26 13 32 0 Lu [19] Covert picture naming > passive viewing 9 9 46 46 ...
Article
Full-text available
Background: Stuttering is characterized by dysfluency and difficulty in speech production. Previous research has found abnormalities in the neural function of various brain areas during speech production tasks. However, the cognitive neural mechanism of stuttering has still not been fully determined. Method: Activation likelihood estimation analysis was performed to provide neural imaging evidence on neural bases by reanalyzing published studies. Results: Our analysis revealed overactivation in the bilateral posterior superior temporal gyrus, inferior frontal gyrus, medial frontal gyrus, precentral gyrus, postcentral gyrus, basal ganglia, and cerebellum, and deactivation in the anterior superior temporal gyrus and middle temporal gyrus among the stutterers. The overactivated regions might indicate a greater demand in feedforward planning in speech production, while the deactivated regions might indicate dysfunction in the auditory feedback system among stutterers. Conclusions: Our findings provide updated and direct evidence on the multi-level impairment (feedforward and feedback systems) of stutterers during speech production and show that the corresponding neural bases were differentiated.
... For example, stutterers fail to show the normal hemispheric asymmetries that are present in prefrontal and occipital lobes (Foundas et al., 2003) or in the frontal operculum and planum temporale (Foundas et al., 2001). Thus, it has been suggested that stutterers may have a different pattern of neural connections compared to fluent speakers (Cykowski et al., 2010;Ludlow and Loucks, 2003;Lu et al., 2010bLu et al., , 2009Salmelin et al., 2000;Sommer et al., 2002;Watkins et al., 2008). ...
... Difficulties in finger-tapping (Smits-Bandstra et al., 2006) and finger movement sequencing (Forster and Webster, 2001) have also been reported. These types of tasks can be considered analogous to motor speech implementation, and probably involve a cortico-basal ganglia-thalamo-cortical circuit and/or a cerebello-cortical circuit that may be defective in stutterers (Lu et al., 2010a(Lu et al., , 2010b(Lu et al., , 2009Smits-Bandstra and De Nil, 2007). However, it should also be considered that these problems could be seen as a consequence in a failure of the recruitment of left frontal regions (Kell et al., 2009). ...
... Connectivity studies in DS support this hypothesis, showing abnormal/weaker connections (Lu et al., 2010b(Lu et al., , 2009Neef et al., 2011a;Salmelin et al., 2000), lower density of white matter fibres (Chang et al., 2011(Chang et al., , 2008Cykowski et al., 2010;Sommer et al., 2002;Watkins et al., 2008), and/or grey matter (Kell et al., 2009) in regions including the left inferior frontal gyrus (Chang et al., 2011;Kell et al., 2009), left motor and premotor regions (Chang et al., 2011;Cykowski et al., 2010) and the bilateral corticospinal tract (Chang et al., 2008). However, patterns of abnormally increased white matter fibres in neighbouring regions have also been reported (Kell et al., 2009;Watkins et al., 2008), including the right hemisphere (Chang et al., 2011(Chang et al., , 2008. ...
Article
Introduction: Developmental stuttering (DS) is viewed as a motor speech-specific disorder, although several lines of research suggest that DS is a symptom of a broader motor disorder. We investigated corticospinal excitability in adult DS and normal speakers. Methods: Transcranial magnetic stimulation (TMS) was administered over left/right hand representation of the motor cortex while recording motor evoked potentials (MEPs) from the contralateral first dorsal interosseous (FDI) muscle. Resting, active motor thresholds, silent period threshold and duration were measured. A stimulus-response curve at resting was also obtained to evaluate MEP amplitudes. Results: Lower corticospinal responses in the left hemisphere of DS were found, as indicated by a reduction of peak-to-peak MEP amplitudes compared to normal speakers. Conclusions: This provides further evidence that DS may be a general motor deficit that also involves motor non-speech-related structures. Moreover, our results confirm that DS may be related to left hemisphere hypoactivation and/or lower left hemisphere dominance. The present data and protocol may be useful for diagnosis of subtypes of DS that may benefit from pharmacological treatment by targeting the general level of cortical excitability.
... The mechanisms of fluency-inducing treatment are hypothesized to be right hemisphere mobilization and restoration of left-hemispheric lateralization of activations [11,25,26,27]. Additionally, during speech, stuttering subjects show decreased functional connectivity (FC) between the left BA44 and left premotor regions and increased FC among homologous right-hemispheric structures [28], as well as abnormal effective connectivity among speech, motor and auditory areas [29,30,31,32]. Several previous studies have also investigated resting-state cerebral blood flow (CBF) in stuttering subjects [12,33,34]. ...
... Moreover, this reduction is positively correlated with stuttering severity, suggesting a possible origin of this disorder [27]. Normal left IFG activation during speech tasks in fluent speakers is either restricted to a small region [12] or absent [29,31] in stuttering subjects. Unexpectedly, we found increased ALFF in this region in stuttering subjects, suggesting abnormal resting-state brain activity, although we do not know whether it is a reflection of disorder origin or compensation. ...
... Anatomically, the left and right planum temporale (PT) show increased gray matter density [6] or volume [4] and atypical (rightward) asymmetry [3,4] in stuttering subjects. Functionally, stuttering subjects have decreased regional cerebral blood flow (rCBF) [12], [67], reduced activation [10,18,29,31], and enhanced mismatch negativity (MMN) event-related brain potential [68] in the left auditory cortex during speech tasks, suggesting a left lateralized auditory perceptual deficit that seems to underlie speech production disorder. Further support for this inference comes from studies that altered auditory feedback (delayed or frequency-shifted) reduced dysfluency in stuttering subjects by increasing auditory cortex rCBF or activation [10,12]. ...
Article
Full-text available
Although developmental stuttering has been extensively studied with structural and task-based functional magnetic resonance imaging (fMRI), few studies have focused on resting-state brain activity in this disorder. We investigated resting-state brain activity of stuttering subjects by analyzing the amplitude of low-frequency fluctuation (ALFF), region of interest (ROI)-based functional connectivity (FC) and independent component analysis (ICA)-based FC. Forty-four adult males with developmental stuttering and 46 age-matched fluent male controls were scanned using resting-state fMRI. ALFF, ROI-based FCs and ICA-based FCs were compared between male stuttering subjects and fluent controls in a voxel-wise manner. Compared with fluent controls, stuttering subjects showed increased ALFF in left brain areas related to speech motor and auditory functions and bilateral prefrontal cortices related to cognitive control. However, stuttering subjects showed decreased ALFF in the left posterior language reception area and bilateral non-speech motor areas. ROI-based FC analysis revealed decreased FC between the posterior language area involved in the perception and decoding of sensory information and anterior brain area involved in the initiation of speech motor function, as well as increased FC within anterior or posterior speech- and language-associated areas and between the prefrontal areas and default-mode network (DMN) in stuttering subjects. ICA showed that stuttering subjects had decreased FC in the DMN and increased FC in the sensorimotor network. Our findings support the concept that stuttering subjects have deficits in multiple functional systems (motor, language, auditory and DMN) and in the connections between them.
... Adults who stutter (AWS) show overactivations in regions of the right hemisphere such as the inferior frontal cortex (IFC) and anterior insula, but lower activations in regions of the left hemisphere such as the left IFC and temporal cortex, compared to fluent con-trols in several speech production and auditory perception tasks (Brown, Ingham, Ingham, Laird, & Fox, 2005;De Nil et al., 2008;Jiang, Lu, Peng, Zhu, & Howell, 2012;Lu et al., 2016). AWS also show altered connectivity between the basal ganglia/cerebellum and cortical brain regions compared to fluent controls in speech production tasks (Chang, Horwitz, Ostuni, Reynolds, & Ludlow, 2011;Howell, Jiang, Peng, & Lu, 2012b;Jiang et al., 2012;Lu et al., 2009;. Moreover, the abnormal brain activation in the left hemisphere and altered connectivity in the circuits between basal ganglia and cerebral cortex have been confirmed in children who stutter in auditory speech processing tasks or in the resting-state condition, but the right hemispheric abnormalities have not (Chang & Zhu, 2013;Sato et al., 2011). ...
... However, EXPLAN lacked imaging evidence that directly supported the model. Consequently, a dual-route neural model was developed and tested empirically in classic speech production tasks (i.e., overt and covert picture naming tasks) Lu et al., 2009;. This dual-route model assumed that two neural circuits were impaired in AWS: (1) the connectivity in the basal ganglia-IFC circuit was altered and this was closely associated with atypical linguistic planning; (2) the connectivity in the cerebellum-PMA circuit was affected and this was associated with atypical speech motor execution (Howell et al., 2012b;Jiang et al., 2012;Lu et al., 2009;. ...
... Consequently, a dual-route neural model was developed and tested empirically in classic speech production tasks (i.e., overt and covert picture naming tasks) Lu et al., 2009;. This dual-route model assumed that two neural circuits were impaired in AWS: (1) the connectivity in the basal ganglia-IFC circuit was altered and this was closely associated with atypical linguistic planning; (2) the connectivity in the cerebellum-PMA circuit was affected and this was associated with atypical speech motor execution (Howell et al., 2012b;Jiang et al., 2012;Lu et al., 2009;. The dual-route model also hypothesized that improvement in linguistic planning (particularly phonological processing) and articulatory motor execution and repair of both the basal ganglia-IFC and cerebellum-PMA circuits are probably essential for full recovery from stuttering in adulthood. ...
... This revealed that there were overactivations in some motor areas (primary and Supplementary motor areas motor areas), right frontal operculum/anterior insula, and right cerebellum, and underactivity in the auditory cortex in PWS (Brown et al., 2005). Other studies have reported higher or lower activity in the basal ganglia of PWS as compared to fluent speakers (Lu et al., 2010a(Lu et al., , 2009(Lu et al., , 2010bWu et al., 1995Wu et al., , 1997. The activity of the basal ganglia also correlated significantly with stuttering severity level (Giraud et al., 2008). ...
... Increase in gray matter volume concentration in the right basal ganglia has also been found in PWS over that observed in fluent speakers (Lu et al., 2010b). Besides regional activity differences, research has also shown altered functional or structural connections or reversed activity-sequencing between the left inferior frontal cortex (IFC) and the frontal motor areas, especially the regions for the face and larynx (Chang, Erickson, Ambrose, Hasegawa-Johnson, & Ludlow, 2008;Chang, Horwitz, Ostuni, Reynolds, & Ludlow, 2011;Cykowski, Fox, Ingham, Ingham, & Robin, 2010;Lu et al., 2010aLu et al., , 2009Salmelin, Schnitzler, Schmitz, & Freund, 2000;Sommer, Koch, Paulus, Weiller, & Buchel, 2002;Watkins, Smith, Davis, & Howell, 2008). Recently, studies have looked at linguistic control separately from motor control in PWS. ...
... The results confirmed that PWS had speech-motor control problems (Chang, Kenney, Loucks, & Ludlow, 2009;Lu et al., 2010a). An additional finding was that the problems were associated with altered connectivity between the motor cortex and the cerebellum (Lu et al., 2010a(Lu et al., , 2009). ...
... There have been a total of 23 fMRI studies of AWS (Preibisch et al., 2003; Van Borsel et al., 2003; Blomgren et al., 2004; Neumann et al., 2004 Neumann et al., , 2005 Giraud et al., 2008; Watkins et al., 2008; DeNil et al., 2008; Sakai et al., 2009; Lu et al., 2009 Lu et al., , 2010a Chang et al., 2009; Kell et al., 2009; Chang et al., 2011; Toyomura et al., 2011; Loucks et al., 2011; Xuan et al., 2012; Jiang et al., 2012; Howell et al., 2012; Wymbs et al., 2013; Liu et al., 2014; Toyomura et al., 2015), and only two published studies using fNIRS with AWS (Sato et al., 2011; Tellis et al., 2015). Sato et al., in addition, also examine brain activity of a mixed group of AWS and CWS. ...
... The right inferior frontal gyrus (IFG) is a cortical structure often implicated in the etiology of stuttering (Brown et al., 2005; but see Budde et al., 2014). This region was shown to be overactive in AWS as compared to AWDS in a variety of speech tasks (Neumann et al., 2005; Lu et al., 2009; Sakai et al., 2009 and see also Neef et al., 2016), with some studies showing higher right IFG activity associated with lower rates of dysfluency (Preibisch et al., 2003; Kell et al., 2009; Braun et al., 1997). This finding lead Preibisch and colleagues to propose that right IFG is involved in compensation for stuttering, possibly substituting for impaired networks in the left hemisphere. ...
... Based on this finding, Lu et al. (2010b) suggested that these regions were unable to receive proper timing signals from the basal ganglia. (Lu et al., 2009) performed connectivity analysis on a much larger network of regions involved in speech production, this time using a covert rather than an overt picture-naming task. The output of the left superior temporal gyrus to the left IFG was the same between AWS and AWDS groups, supporting the idea that processes for retrieving the phonological code for an intended utterance are intact in AWS. ...
Article
Full-text available
Purpose: Stuttering is a disorder that affects millions of people all over the world. Over the pasttwo decades, there has been a great deal of interest in investigating the neural basis of the disorder. This systematic literature review is intended to provide a comprehensive summary of theneuroimaging literature on developmental stuttering. It is a resource for researchers to quicklyand easily identify relevant studies for their areas of interest and enable them to determine themost appropriate methodology to utilize in their work. The review also highlights gaps in the literature in terms of methodology and areas of research. Methods: We conducted a systematic literature review on neuroimaging studies on developmental stuttering according to the PRISMA guidelines. We searched for articles in the pubmed database containing "stuttering" OR "stammering" AND either "MRI", "PET", "EEG", "MEG", "TMS"or "brain" that were published between 1995/ 01/ 01 and 2016/ 01/ 01. Results: The search returned a total of 359 items with an additional 26 identified from a manualsearch. Of these, there were a total of 111 full text articles that met criteria for inclusion in thesystematic literature review. We also discuss neuroimaging studies on developmental stutteringpublished throughout 2016. The discussion of the results is organized first by methodology andsecond by population (i.e., adults or children) and includes tables that contain all items returnedby the search. Conclusions: There are widespread abnormalities in the structural architecture and functional organization of the brains of adults and children who stutter. These are evident not only in speechtasks, but also non-speech tasks. Future research should make greater use of functional neuroimaging and noninvasive brain stimulation, and employ structural methodologies that havegreater sensitivity. Newly planned studies should also investigate sex differences, focus on augmenting treatment, examine moments of dysfluency and longitudinally or cross-sectionally investigate developmental trajectories in stuttering.
... Ackermann & Riecker, 2011;Belyk et al., 2015Belyk et al., , 2017Brown et al., 2005;Budde et al., 2014;Chang, 2014;Chang et al., 2019;Etchell et al., 2014Etchell et al., , 2018Neef, Anwander et al., 2015). TMS, EEG (other than Busan et al., 2019), tDCS, and MEG data have been not included in the Chang et al., 2009De Nil et al., 2000Fox et al., 1996Fox et al., 2000Ingham et al., 2000Ingham et al., 2004Ingham et al., 2012Sakai et al., 2009Stager et al., 2003Toyomura et al., 2011Chang et al., 2011Lu et al., 2009Busan et al., 2019a Kell et al., 2018Ingham et al., 2012Desai et al., 2017Lu et al., 2012Lu et al., 2016Qiao et al., 2017Xuan et al., 2012Yang et al. 2016Abe et al., 1992Abe et al., 1993Ackermann et al., 1996Alexander et al., 1987 neurosurgery patients, in speech motor disturbances such as speech arrests, stuttering, or vocalizations. In this context, Misaghi, Zhang, Gracco, De Nil & Beal (2018) reported higher fractional anisotropy and higher axial diffusivity in the right FAT of children who stutter, thus suggesting a higher functionality of this tract. ...
... When considering the functionality of SMA connections during motor and speech tasks, showed that during speech (i.e. a picturenaming task) stuttering may be characterized by stronger connectivity flowing from the basal ganglia to the thalamus, as well as from the thalamus to the pre-SMA. Lu et al. (2009) used a covert naming task to show that DS was characterized by positive connections among the SMA "complex" and diffuse networks of brain regions such as the right precentral gyrus and right superior frontal gyrus. Negative projections to the left inferior frontal gyrus were also evident, as well as positive connections to the left temporal cortex (in general, abnormal patterns of connection with bilateral temporal cortices were observed). ...
... Ludlow & Loucks, 2003), mainly based on dysfunctional long-range neural networks (e.g. Lu et al., 2009), the role of the SMA "complex" (i.e. a region useful to integrate different neural signals and connecting different neural networks) may assume greater importance with respect to classical models of stuttering physiopathology. This suggestion is also justified by the available observations about the extended range of "functional" connectivity of the SMA in healthy humans, ranging from fronto-parietal regions to the sensorimotor and temporal cortex in both hemispheres (this is evident even for "deeper" regions such as basal ganglia and cingulate cortex; Kim et al., 2010). ...
Article
Developmental stuttering is a frequent neurodevelopmental disorder with a complex neurobiological basis. Robust neural markers of stuttering include imbalanced activity of speech and motor related brain regions, and their impaired structural connectivity. The dynamic interaction of cortical regions is regulated by the cortico-basal ganglia-thalamo-cortical system with the supplementary motor area constituting a crucial cortical site. The SMA integrates information from different neural circuits, and manages information about motor programs such as self-initiated movements, motor sequences, and motor learning. Abnormal functioning of SMA is increasingly reported in stuttering, and has been recently indicated as an additional “neural marker” of DS: anatomical and functional data have documented abnormal structure and activity of the SMA, especially in motor and speech networks. Its connectivity is often impaired, especially when considering networks of the left hemisphere. Compatibly, recent data suggest that, in DS, SMA is part of a poorly synchronized neural network, thus resulting in a likely substrate for the appearance of DS symptoms. However, as evident when considering neural models of stuttering, the role of SMA has not been fully clarified. Herein, the available evidence is reviewed, which highlights the role of the SMA in DS as a neural “hub”, receiving and conveying altered information, thus “gating” the release of correct or abnormal motor plans.
... The probe geometry consisted of 36 channels covering parts of the frontal, motor, parietal, and temporal cortices (see Fig. 2). These regions were selected based on the results of six published research reports that used fMRI to examine speech production in AWS Preibisch et al., 2003;Watkins et al., 2008;Chang et al., 2009;Lu et al., 2009Lu et al., , 2010a. Regions were averaged into a single ROI if their coordinates were within one centimeter of one another. ...
... We found higher neural activation in the L-IFG in CON with higher planning load but no such change in neural activation for AWS. The atypical activation of L-IFG during speechmotor planning is consistent with previous functional imaging studies of AWS (Braun et al., 1997;Neumann et al., 2003;De Nil et al., 2008;Watkins et al., 2008;Lu et al., 2009Lu et al., , 2010a. It is also well documented that the anatomical development of L-IFG is atypical in children who stutter as young as 3 to 7-years-old (Chang et al., 2008;Beal et al., 2013;Garnett et al., 2018) and continues along an abnormal trajectory into middle-age adulthood for those with persistent forms of the disorder (Beal et al., 2015). ...
... This has the advantage of direct comparisons with previous PET/fMRI research. The group-level results are in agreement with previous PET/fMRI studies that show widespread differences between AWS and CON in bilateral frontal, motor, parietal, and temporal network activation patterns during the overt and covert production of single words or short utterances (De Nil et al., 2000Chang et al., 2009;Lu et al., 2009Lu et al., , 2010aLoucks et al., 2011). Although there are important planning versus execution task-based differences, in general the AWS exhibited over-activation in right hemisphere regions including R-IFG, R-MFG, R-postCG, and R-SMG, and under-activation in left hemisphere networks including L-IFG, and L-pre-and postCG for simple non-word and word production. ...
Article
Our study aimed to determine the neural correlates of speech planning and execution in adults who stutter (AWS). Fifteen AWS and 15 controls (CON) completed two tasks that either manipulated speech planning or execution processing loads. Functional near-infrared spectroscopy (fNIRS) was used to measure changes in blood flow concentrations during each task, thus providing an indirect measure of neural activity. An image-based reconstruction technique was used to analyze the results and facilitate their interpretation in the context of previous functional neuroimaging studies of AWS that used positron emission tomography (PET) or functional magnetic resonance imaging (fMRI). For planning, we compared neural activity associated with high versus low planning load in AWS and CON. For execution, we compared the neural activity associated with overt versus covert naming in AWS and CON. Broadly, group level effects corroborate previous PET/fMRI findings including under-activation in left-hemisphere perisylvian speech-language networks and over-activation in right-hemisphere homologs. Increased planning load revealed atypical left-hemisphere activation in AWS, whereas increased execution load yielded atypical right fronto-temporo-parietal and bilateral motor activation in AWS. Our results add to the limited literature differentiating speech planning versus execution processes in AWS.
... By contrasting the PPI results from the PWS and controls, Chang and colleagues revealed that the speech-related increased in functional connectivity between left BA44 (the seed region) and right STG (among other target brain areas) was significantly weaker in PWS than in controls. Lu et al. (2009) used probabilistic ICA (PICA) and structural equation modeling (SEM) to study the differences between PFS and normal speakers in a large-scale functional connectivity patterns during speech production. The results of the PICA analysis differed vastly between the stutterers and nonstutterers. ...
... och et al. 2007). In this regard, it is noteworthy that a previous study found GM volume reduction in the cerebellum in PWS (based on VBM, Song et al. 2007) and another previous study showed abnormal functional connectivity between the right cerebellum and cerebral cortical areas, including the bilateral precentral gyri and the right angular gyrus (Lu et al . 2009). Also, it is worth pointing out that most previous behavioral studies investigated millisecond motor timing by using relatively simple tasks such as finger tapping. The nature of these simple actions may belie the true neural substrate of millisecond motor timing in speech production, which involves much more complex movements and rich ...
... This distinctive course yields prevalence rates that vary with age, with approximately 5% of children and 1% of adults meeting diagnostic criteria for stuttering [1,2]. The precise etiology of stuttering remains largely unknown, although recent neuroimaging studies have provided evidence for abnormal changes of volumes and function in widely distributed regions involved in the production of speech [3][4][5][6][7][8][9][10][11][12][13][14]. ...
... Brain regions that subserve self-regulatory processes in the Simon task, including the ACC, adjacent motor areas, and DLPFC, also support the production of normal speech [44][45][46][47][48], and we hypothesize that disturbances in self-regulatory control over speech functions contribute importantly to dysfluent speech in persons who stutter. Consistent with this hypothesis, prior studies have identified in stuttering speakers reduced blood flow to the ACC at rest and abnormalities of functional connectivity in motor cortices, basal ganglia, Broca's area, and neighboring regions during speech tasks [4,10,12,49]. Therefore, we suspect that the functional abnormalities we observed in the ACC and DLPFC during the Simon task likely represent disturbances in selfregulatory capacities that contribute to dysfluent speech in persons who stutter. ...
... Affected connections might impede the signal transfer between language-related and speech-related left fronto-parieto-temporal brain regions as summarized in a recent quantitative review (Neef et al. 2015a). Fluent speech production evolves from dynamic network organizations, but functional connectivity within these networks is aberrant in those who stutter (Lu et al. 2009(Lu et al. , 2010aChang et al. 2011;Chang and Zhu 2013). The spatio-temporal patterning, and particularly the timing of neuronal signals guiding fluent speech production, is not sufficiently tuned (Kent 2000;Salmelin et al. 2000;Ludlow and Loucks 2003;Alm 2004;Etchell et al. 2014). ...
... During a reading task, activity of the caudate nucleus correlated positively with stuttering severity, while a negative correlation between activity in the substantia nigra and degree of stuttering severity is reported for both pre-and post-treatment (Giraud et al. 2008). Altered functional connectivity between basal ganglia and cortical regions has been observed (Lu et al. 2009(Lu et al. , 2010aChang and Zhu 2013), and disturbed structural connectivity between cortical and subcortical regions has also been reported (Watkins et al. 2008;Connally et al. 2014;Chang et al. 2015). ...
Article
Full-text available
Persistent developmental stuttering is associated with basal ganglia dysfunction or dopamine dysregulation. Here, we studied whole-brain functional connectivity to test how basal ganglia structures coordinate and reorganize sensorimotor brain networks in stuttering. To this end, adults who stutter and fluent speakers (control participants) performed a response anticipation paradigm in the MRI scanner. The preparation of a manual Go/No-Go response reliably produced activity in the basal ganglia and thalamus and particularly in the substantia nigra. Strikingly, in adults who stutter, substantia nigra activity correlated positively with stuttering severity. Furthermore, functional connectivity analyses yielded altered task-related network formations in adults who stutter compared to fluent speakers. Specifically, in adults who stutter, the globus pallidus and the thalamus showed increased network synchronization with the inferior frontal gyrus. This implies dynamic shifts in the response preparation-related network organization through the basal ganglia in the context of a non-speech motor task in stuttering. Here we discuss current findings in the traditional framework of how D1 and D2 receptor activity shapes focused movement selection, thereby suggesting a disproportional involvement of the direct and the indirect pathway in stuttering. Electronic supplementary material The online version of this article (doi:10.1007/s00429-017-1476-1) contains supplementary material, which is available to authorized users.
... In particular our findings of increased recruitment of premotor and motor regions in stuttering relative to fluent controls during self-formulated speech replicated previous work using similar paradigms [39] [123]. Our general findings of decreased activation in sentence reading are also somewhat consistent with the literature [249], though reductions in stuttering are most common during single-word production [178][54] [153][151] [117]. ...
... Finally, our observations during sentence reading, of increased central opercular activation in adults who stutter, are largely consistent with most of the literature. The exceptions are studies that combined or contrasted natural speech and fluency enhancement conditions [249] [122] and studies that examined activation during single-word production [178][54] [153][151] [117] [70]. Overall, trait differences between adults who stutter and fluent adults were specific to the tasks examined in our study, as were similarities to the literature. ...
Thesis
Full-text available
The aim of this thesis was to investigate the neural underpinnings of persistent developmental stuttering. We explored neural systems important for speech-motor integration and focused on subcortical control systems: the basal ganglia and cerebellum. A secondary aim of this work was to distinguish effects related to general traits of the disorder from those reflecting specific states of stuttered speech. To address these aims we used a variety of neuroimaging methodologies as well as an extensive neuropsychological and empirical test battery. Our examination of neural pathway microstructure using diffusion-tensor imaging replicated previous findings of widespread disorganisation of white matter in people who stutter. This disruption included all major white matter pathways leading in and out of the cerebellum. In our second, third, and fourth studies we examined functional activity at rest and during different types of speech. The brain networks used by people who stutter and controls largely overlapped. The brain regions that distinguished general traits and specific states of stuttering were somewhat task-specific. Subcortical activation in the basal ganglia and cerebellum was related to the frequency of dysfluent speech in the scanner. In our final study we examined performance on a variety of classical tasks of motor learning. We observed evidence of delayed learning in response to changes in environmental feedback in the stuttering group relative to controls. Within people who stutter, subgroups who differ according to heritability of the disorder may also differ in the balance of dopamine in the basal ganglia. Overall, we concluded that cerebellar alterations contribute to the general trait of stuttering, while basal ganglia disruption may reflect specific effects within stuttering. Our work supports a broader role of the subcortical system in speech production, generally.
... These ''neural markers" may be a consequence of abnormal modulations in intracortical motor networks as demonstrated by TMS experiments (Busan et al., 2017(Busan et al., , 2016(Busan et al., , 2009Neef et al., 2015aNeef et al., , 2015bNeef et al., , 2011Whillier et al., 2018). They may also be due to defective white matter, especially in brain regions close to and around the left inferior frontal regions, comprising motor/premotor structures, but also in fibers in longrange neural pathways directed toward muscular effectors (Lu et al. 2009;Sommer et al., 2002;Watkins et al., 2008). Finally, other evidence has suggested that DS is related to a defective cortico-basal-thalamo-cortical system (Alm, 2004;Craig-McQuaide et al., 2014) and to dopamine over-activation in the basal ganglia (Wu et al., 1997). ...
... The present observation of an initial lack of activation in the SMA ''complex", followed by higher activations of premotor regions of the right hemisphere after about 400 ms from it, sustain this possibility. Basal ganglia dysfunction is also commonly reported in DS (Alm, 2004;Craig-McQuaide et al., 2014), resulting in lower connectivity of related circuits, including SMA (Chang and Zhu, 2013;Chang et al., 2016) and influencing motor and/or large-scale networks (Cantello et al., 2002;Lu et al., 2010bLu et al., , 2009Metzger et al., 2018;Yang et al., 2016;Ziemann et al., 1997). Smaller cerebral volumes may be evident after basal ganglia lesions in the SMA (Exner et al., 2002). ...
Article
Objective: Brain dynamics in developmental stuttering (DS) are not well understood. The supplementary motor area (SMA) plays a crucial role, since it communicates with regions related to planning/execution of movements, and with sub-cortical regions involved in paced/voluntary acts (such as speech). We used TMS combined with EEG to shed light on connections in DS, stimulating the SMA. Methods: TMS/EEG was recorded in adult DS and fluent speakers (FS), stimulating the SMA during rest. TMS-evoked potentials and source distribution were evaluated. Results: Compared to FS, stutterers showed lower activity of neural sources in early time windows: 66-82 ms in SMA, and 91-102 ms in the left inferior frontal cortex and left inferior parietal lobule. Stutterers, however, showed higher activations in later time windows (i.e. from 260-460 ms), in temporal/premotor regions of the right hemisphere. Conclusions: These findings represent the functional counterpart to known white matter and cortico-basal-thalamo-cortical abnormalities in DS. They also explain how white matter abnormalities and cortico-basal-thalamo-cortical dysfunctions may be associated in DS. Finally, a mechanism is proposed in which compensatory activity of the non-dominant (right) hemisphere is recruited. Significance: DS may be a disorder of neural timing that appears to be delayed compared to FS; new mechanisms that support stuttering symptoms are inferred; the SMA may be a promising target for neuro-rehabilitation.
... This distinctive course yields prevalence rates that vary with age, with approximately 5% of children and 1% of adults meeting diagnostic criteria for stuttering [1,2]. The precise etiology of stuttering remains largely unknown, although recent neuroimaging studies have provided evidence for abnormal changes of volumes and function in widely distributed regions involved in the production of speech [3][4][5][6][7][8][9][10][11][12][13][14]. ...
... Brain regions that subserve self-regulatory processes in the Simon task, including the ACC, adjacent motor areas, and DLPFC, also support the production of normal speech [44][45][46][47][48], and we hypothesize that disturbances in self-regulatory control over speech functions contribute importantly to dysfluent speech in persons who stutter. Consistent with this hypothesis, prior studies have identified in stuttering speakers reduced blood flow to the ACC at rest and abnormalities of functional connectivity in motor cortices, basal ganglia, Broca's area, and neighboring regions during speech tasks [4,10,12,49]. Therefore, we suspect that the functional abnormalities we observed in the ACC and DLPFC during the Simon task likely represent disturbances in selfregulatory capacities that contribute to dysfluent speech in persons who stutter. ...
Article
Full-text available
Developmental stuttering is a disorder of speech fluency with an unknown pathogenesis. The similarity of its phenotype and natural history with other childhood neuropsychiatric disorders of frontostriatal pathology suggests that stuttering may have a closely related pathogenesis. We investigated in this study the potential involvement of frontostriatal circuits in developmental stuttering. We collected functional magnetic resonance imaging data from 46 persons with stuttering and 52 fluent controls during performance of the Simon Spatial Incompatibility Task. We examined differences between the two groups of blood-oxygen-level-dependent activation associated with two neural processes, the resolution of cognitive conflict and the context-dependent adaptation to changes in conflict. Stuttering speakers and controls did not differ on behavioral performance on the task. In the presence of conflict-laden stimuli, however, stuttering speakers activated more strongly the cingulate cortex, left anterior prefrontal cortex, right medial frontal cortex, left supplementary motor area, right caudate nucleus, and left parietal cortex. The magnitude of activation in the anterior cingulate cortex correlated inversely in stuttering speakers with symptom severity. Stuttering speakers also showed blunted activation during context-dependent adaptation in the left dorsolateral prefrontal cortex, a brain region that mediates cross-temporal contingencies. Frontostriatal hyper-responsivity to conflict resembles prior findings in other disorders of frontostriatal pathology, and therefore likely represents a general mechanism supporting functional compensation for an underlying inefficiency of neural processing in these circuits. The reduced activation of dorsolateral prefrontal cortex likely represents the inadequate readiness of stuttering speakers to execute a sequence of motor responses.
... Speech and general motor programming deficits have both been reported in people who stutter (PWS) (Fox et al., 1996;Stager et al., 2005;De Nil et al., 2008;Lu et al., 2010a;Smith et al., 2012;Smits-Bandstra and De Nil, 2013;Smits-Bandstra and Gracco, 2015). With respect to speech deficits, speech production difficulties are apparent in PWS and are associated with anomalous neural functional activity in various brain areas (Fox et al., 1996;Braun et al., 1997;Ingham et al., 2000;Stager et al., 2003;De Nil et al., 2008;Watkins et al., 2008;Chang et al., 2009;Kell et al., 2009;Lu et al., 2009Lu et al., , 2010bJiang et al., 2012;Cai et al., 2014;Belyk et al., 2015). PWS and controls also show behavioral and neural functional activity differences during speech perception (Weber- Fox et al., 2008;Liotti et al., 2010;Sato et al., 2011;Jansson-Verkasalo et al., 2014;Pelczarski and Yaruss, 2014). ...
... The left IFC/anterior insula showed increased neural activity when the condition changed from SN to LN in the controls, but not in PWS. Anomalous neural activity in this area or connectivity between this area and the motor and auditory areas have been reported previously in various speech production tasks in adult PWS (Lu et al., 2009(Lu et al., , 2010aJiang et al., 2012;Kell, 2014). Most importantly, the current results indicated that this area failed to respond to the manipulation of computational load in the speech production task in PWS. ...
Article
Full-text available
Speech production difficulties are apparent in people who stutter (PWS). PWS also have difficulties in speech perception compared to controls. It is unclear whether the speech perception difficulties in PWS are independent of, or related to, their speech production difficulties. To investigate this issue, functional MRI data were collected on 13 PWS and 13 controls whilst the participants performed a speech production task and a speech perception task. PWS performed poorer than controls in the perception task and the poorer performance was associated with a functional activity difference in the left anterior insula (part of the speech motor area) compared to controls. PWS also showed a functional activity difference in this and the surrounding area [left inferior frontal cortex (IFC)/anterior insula] in the production task compared to controls. Conjunction analysis showed that the functional activity differences between PWS and controls in the left IFC/anterior insula coincided across the perception and production tasks. Furthermore, Granger Causality Analysis on the resting-state fMRI data of the participants showed that the causal connection from the left IFC/anterior insula to an area in the left primary auditory cortex (Heschl’s gyrus) differed significantly between PWS and controls. The strength of this connection correlated significantly with performance in the perception task. These results suggest that speech perception difficulties in PWS are associated with anomalous functional activity in the speech motor area, and the altered functional connectivity from this area to the auditory area plays a role in the speech perception difficulties of PWS.
... Decades of neuroimaging research have revealed some convergent findings that point to subtle functional (Fox et al., 1996;Braun et al., 1997;Watkins et al., 2008;Chang et al., 2009) and structural (Foundas et al., 2001(Foundas et al., , 2003Sommer et al., 2002;Jancke et al., 2004;Beal et al., 2007Beal et al., , 2012Chang et al., 2008;Watkins et al., 2008) differences in cortical brain areas supporting auditory-motor integration for speech processing. Other studies examining intrinsic functional connectivity of brain activity based on functional MRI data (Lu et al., 2009(Lu et al., , 2010Xuan et al., 2012) and older PET studies (Wu et al., 1995(Wu et al., , 1997, have shown differences involving the basal ganglia-thalamocortical (BGTC) loop. These findings corroborate some interesting phenomena associated with stuttering, such as the fact that auditory masking or manipulation (e.g. ...
... In previous studies examining stuttering speakers, commonly reported results suggested possible deficiencies in connectivity involving the left motor and auditory cortical areas (Lu et al., 2009(Lu et al., , 2012Chang et al., 2011), and increases in structural volume (Foundas et al., 2001) and functional hyperactivity in the right cortical areas (Fox et al., 1996;Braun et al., 1997;De Nil et al., 2000). Given this, we examined network connectivity using bilateral pars opercularis (BA44) and posterior superior temporal gyrus seeds to examine intrinsically correlated brain activity patterns using resting state functional MRI data (Tables 4 and 5). ...
Article
Affecting 1% of the general population, stuttering impairs the normally effortless process of speech production, which requires precise coordination of sequential movement occurring among the articulatory, respiratory, and resonance systems, all within millisecond time scales. Those afflicted experience frequent disfluencies during ongoing speech, often leading to negative psychosocial consequences. The aetiology of stuttering remains unclear; compared to other neurodevelopmental disorders, few studies to date have examined the neural bases of childhood stuttering. Here we report, for the first time, results from functional (resting state functional magnetic resonance imaging) and structural connectivity analyses (probabilistic tractography) of multimodal neuroimaging data examining neural networks in children who stutter. We examined how synchronized brain activity occurring among brain areas associated with speech production, and white matter tracts that interconnect them, differ in young children who stutter (aged 3-9 years) compared with age-matched peers. Results showed that children who stutter have attenuated connectivity in neural networks that support timing of self-paced movement control. The results suggest that auditory-motor and basal ganglia-thalamocortical networks develop differently in stuttering children, which may in turn affect speech planning and execution processes needed to achieve fluent speech motor control. These results provide important initial evidence of neurological differences in the early phases of symptom onset in children who stutter.
... In addition to these task activation analyses, previous studies have examined task-based functional connectivity (i.e., activation coupling between multiple brain areas during a speaking task) differences between AWS and adults who do not stutter (ANS). Some studies show reduced connectivity between the left IFG and the left precentral gyrus in AWS (Chang et al., 2011;Lu et al., 2009), which suggests an impairment in translating speech plans for motor execution (Guenther, 2016). Other studies show group differences in connectivity between auditory, motor, premotor, and subcortical areas (Chang et al., 2011;Kell et al., 2018;Lu et al., 2009;. ...
... Some studies show reduced connectivity between the left IFG and the left precentral gyrus in AWS (Chang et al., 2011;Lu et al., 2009), which suggests an impairment in translating speech plans for motor execution (Guenther, 2016). Other studies show group differences in connectivity between auditory, motor, premotor, and subcortical areas (Chang et al., 2011;Kell et al., 2018;Lu et al., 2009;. Results of these task-based connectivity studies, as well as restingstate and structural connectivity studies (e.g., Chang & Zhu, 2013;Sitek et al., 2016), have made it apparent that stuttering behavior is not merely the result of disruptions to one or more separate brain regions, but also differences in the ability for brain regions to communicate with one another during speech. ...
Article
Purpose Stuttering is characterized by intermittent speech disfluencies, which are dramatically reduced when speakers synchronize their speech with a steady beat. The goal of this study was to characterize the neural underpinnings of this phenomenon using functional magnetic resonance imaging. Method Data were collected from 16 adults who stutter and 17 adults who do not stutter while they read sentences aloud either in a normal, self-paced fashion or paced by the beat of a series of isochronous tones (“rhythmic”). Task activation and task-based functional connectivity analyses were carried out to compare neural responses between speaking conditions and groups after controlling for speaking rate. Results Adults who stutter produced fewer disfluent trials in the rhythmic condition than in the normal condition. Adults who stutter did not have any significant changes in activation between the rhythmic condition and the normal condition, but when groups were collapsed, participants had greater activation in the rhythmic condition in regions associated with speech sequencing, sensory feedback control, and timing perception. Adults who stutter also demonstrated increased functional connectivity among cerebellar regions during rhythmic speech as compared to normal speech and decreased connectivity between the left inferior cerebellum and the left prefrontal cortex. Conclusions Modulation of connectivity in the cerebellum and prefrontal cortex during rhythmic speech suggests that this fluency-inducing technique activates a compensatory timing system in the cerebellum and potentially modulates top-down motor control and attentional systems. These findings corroborate previous work associating the cerebellum with fluency in adults who stutter and indicate that the cerebellum may be targeted to enhance future therapeutic interventions. Supplemental Material https://doi.org/10.23641/asha.14417681
... The neuroimaging research shows that patients with stuttering have functional anomalies in the right frontal operculum/anterior insula, temporal areas, basal ganglia, and cerebellum [3,[16][17][18][19][20][21][22][23]. Patients who stutter also show altered connectivity between the basal ganglia/cerebellum and the cortical areas, and among different cortical areas [3,4,24,25]. Studies that have examined brain structural anomalies have identified several anomalous brain regions, especially the left inferior frontal cortex (IFC), in persistent devleopmental stuttering [26][27][28][29][30]. ...
... A significant correlation between activity in the basal ganglia and stuttering severity level has also been reported [18]. Similarly, the overactivation of the right cerebellum has been identified as one of the three neural signatures of stuttering [16] and was identified as specific to overt stuttered speech [25,58,59]. Furthermore, stuttering patients showed altered functional connectivity between the putamen/cerebellum and the cortical motor areas to controls [3,4]. ...
Article
Full-text available
Among the non-fluencies seen in speech, some are more typical (MT) of stuttering speakers, whereas others are less typical (LT) and are common to both stuttering and fluent speakers. No neuroimaging work has evaluated the neural basis for grouping these symptom types. Another long-debated issue is which type (LT, MT) whole-word repetitions (WWR) should be placed in. In this study, a sentence completion task was performed by twenty stuttering patients who were scanned using an event-related design. This task elicited stuttering in these patients. Each stuttered trial from each patient was sorted into the MT or LT types with WWR put aside. Pattern classification was employed to train a patient-specific single trial model to automatically classify each trial as MT or LT using the corresponding fMRI data. This model was then validated by using test data that were independent of the training data. In a subsequent analysis, the classification model, just established, was used to determine which type the WWR should be placed in. The results showed that the LT and the MT could be separated with high accuracy based on their brain activity. The brain regions that made most contribution to the separation of the types were: the left inferior frontal cortex and bilateral precuneus, both of which showed higher activity in the MT than in the LT; and the left putamen and right cerebellum which showed the opposite activity pattern. The results also showed that the brain activity for WWR was more similar to that of the LT and fluent speech than to that of the MT. These findings provide a neurological basis for separating the MT and the LT types, and support the widely-used MT/LT symptom grouping scheme. In addition, WWR play a similar role as the LT, and thus should be placed in the LT type.
... neurophysiological (Blomgren et al., 2003;Braun et al., 1997;Chang et al., 2009;De Nil et al., 2001;De Nil et al., 2008;Fox et al., 1996;Fox et al., 2000;Giraud et al., 2008;Lu et al., 2009;Watkins et al., 2008) differences have been observed in adults who stutter relative to fluent speakers. To date, only 2 studies have examined the neural correlates of stuttering specifically in children (Chang et al., 2008;Weber-Fox et al., 2008). ...
... Presumably, its interaction with the auditory cortical area and the corticobasal-ganglia loop forms the neural basis of the AF-based online temporal control. Previous MRI studies have reported abnormal functional (Lu et al., 2009) connectivity involving the SMA that are possible correlates of the auditory-motor deficit observed in the PWS by current study, which can be tested in future functional neuroimaging studies that use AF perturbation during connected speech. ...
Article
Auditory feedback (AF), the speech signal received by a speaker's own auditory system, contributes to the online control of speech movements. Recent studies based on AF perturbation provided evidence for abnormalities in the integration of auditory error with ongoing articulation and phonation in persons who stutter (PWS), but stopped short of examining connected speech. This is a crucial limitation considering the importance of sequencing and timing in stuttering. In the current study, we imposed time-varying perturbations on AF while PWS and fluent participants uttered a multisyllabic sentence. Two distinct types of perturbations were used to separately probe the control of the spatial and temporal parameters of articulation. While PWS exhibited only subtle anomalies in the AF-based spatial control, their AF-based fine-tuning of articulatory timing was substantially weaker than normal, especially in early parts of the responses, indicating slowness in the auditory-motor integration for temporal control.
... An additional criterion, 'results reported in terms of univariate contrasts,' was added to address new types of analyses not currently amenable to ALE meta-analysis (e.g. 'feature extraction' in (Lu et al., 2009)). Collectively, these selection criteria eliminated 92 papers, leaving 17 papers eligible for analyses. ...
Article
Developmental stuttering is a speech disorder most likely due to a heritable form of developmental dysmyelination impairing the function of the speech-motor system. Speech-induced brain-activation patterns in persons who stutter (PWS) are anomalous in various ways; the consistency of these aberrant patterns is a matter of ongoing debate. Here, we present a hierarchical series of coordinate-based meta-analyses addressing this issue. Two tiers of meta-analyses were performed on a 17-paper dataset (202 PWS; 167 fluent controls). Four large-scale (top-tier) meta-analyses were performed, two for each subject group (PWS and controls). These analyses robustly confirmed the regional effects previously postulated as “neural signatures of stuttering” (Brown, Ingham, Ingham, Laird, & Fox, 2005) and extended this designation to additional regions. Two smaller-scale (lower-tier) meta-analyses refined the interpretation of the large-scale analyses: (1) a between-group contrast targeting differences between PWS and controls (stuttering trait); and (2) a within-group contrast (PWS only) of stuttering with induced fluency (stuttering state).
... At the time of writing, we are unaware of any studies directly examining changes in functional connectivity with AOS. The disorder of stuttering, however, has received some attention and studies are demonstrating both functional and structural differences in the speech motor control network relative to nonstuttering speakers (e.g, Sommer et al., 2002;Watkins et al., 2007;Lu et al., 2009Lu et al., , 2010Cykowski et al., 2010;Chang et al., 2011;Howell et al., 2012;Xuan et al., 2012;Cai et al., 2014). While stuttering is distinct from AOS, theoretical explanations of the disorder have centered on altered reliance on feedback vs. feedforward motor control, similar to AOS. ...
Article
Full-text available
A critical examination of speech motor control depends on an in-depth understanding of network connectivity associated with Brodmann areas 44 and 45 and surrounding cortices. Damage to these areas has been associated with two conditions-the speech motor programming disorder apraxia of speech (AOS) and the linguistic/grammatical disorder of Broca's aphasia. Here we focus on AOS, which is most commonly associated with damage to posterior Broca's area (BA) and adjacent cortex. We provide an overview of our own studies into the nature of AOS, including behavioral and neuroimaging methods, to explore components of the speech motor network that are associated with normal and disordered speech motor programming in AOS. Behavioral, neuroimaging, and computational modeling studies are indicating that AOS is associated with impairment in learning feedforward models and/or implementing feedback mechanisms and with the functional contribution of BA6. While functional connectivity methods are not yet routinely applied to the study of AOS, we highlight the need for focusing on the functional impact of localized lesions throughout the speech network, as well as larger scale comparative studies to distinguish the unique behavioral and neurological signature of AOS. By coupling these methods with neural network models, we have a powerful set of tools to improve our understanding of the neural mechanisms that underlie AOS, and speech production generally.
... with compelling evidence that this defect or ineffi ciency is associated with defects or ineffi ciencies at the level of the striatum. Lesion studies of neurogenic stuttering (Helm-Estabrooks, 1999;Lundgren, Helm-Estabrooks, & Klein, 2010;Tani & Sakai, 2011) and functional imaging studies of adults with developmental stuttering (Fox, Ingham, Ingham, Hirsch, Downs, Martin, et al., 1996;Braun, Varga, Stager, Schulz, Selbie, Maisog, et al, 1997;Wu, Maguire, Riley, Lee, Keator, Tang, et al., 1997;Giraud, et al., 2008;Lu, Ning, Peng, Ding, Li, Yang, et al., 2009) have shown that the striatum is part of a dysfunctional cortical-subcortical network that may characterize dysfl uency disorders. ...
Article
Full-text available
A temporal motor defect in speech preparation and/or planning may contribute to the development of stuttering. This defect may be linked to a dysfunctional cortical-subcortical network at the level of the striatum. To determine whether structural differences exist and whether group differences are associated with stuttering severity or manual laterality, the caudate was measured in 14 children who stutter (CWS) and in a control group of right-handed boys, ages 8-13 years. There was a statistically significant hemisphere by group effect for caudate volume. CWS had reduced right caudate volume and atypical leftward asymmetry compared to controls. Nine of the 13 CWS with atypical caudate asymmetry had atypical manual laterality. These anomalies may represent a vulnerability that perturbs speech planning/preparation and contributes to inefficiencies in action-perception coupling that may be an indicator of stuttering susceptibility. These results suggest that right-handed boys who stutter may have a defect in the feedforward cortico-striato-thalamo-cortical networks.
... η 2 p = .15). Differences between stuttering and typically fluent speakers in the neural networks supporting self-monitoring of covert speech have also been reported (e.g., Lu et al., 2009). While such findings support a role for verbal monitoring in stuttering, further testing is required to understand the precise role of such skills in fluent speech production, particularly in childhood. ...
Article
Full-text available
We investigated phonemic competence in production in three age groups of children - 7 and 8 years, 10 and 11 years, 12 and 13 years-using rhyme and phoneme monitoring. Participants were required to name target pictures silently while monitoring covert speech for the presence or absence of a rhyme or phoneme match. Performance in the verbal tasks was compared to a nonverbal control task in which participants monitored tone sequence pairs for a pattern match. Repeated measures ANOVA revealed significant differences between the three age groups in phoneme monitoring while similar differences were limited to the younger age groups in rhyme monitoring. This finding supported early and on-going acquisition of rhyme- and later acquisition of segment-level units. In addition, the 7 and 8-year-olds were significantly slower in monitoring phonemes within consonant clusters compared to the 10 and 11-year-olds and in monitoring both singleton phonemes and phonemes within clusters compared to the 12 and 13-year-olds. Regression analysis revealed that age accounted for approximately 30% variance in the nonverbal and 60% variance in the verbal monitoring tasks. We attribute the observed differences to the emergence of cognitive processes such as segmentation skills that are critical to performing the verbal monitoring tasks.
... This could be consistent with the evidence of cerebellar overactivity in PWS reported by Brown et al. (2005). Structural equation modeling (SEM) also provides evidence of altered connectivity in the basal ganglia-thalamo-cortical circuit in PWS (Lu et al., 2009;Civier et al., 2013). ...
Article
Full-text available
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.
... Interestingly, greater stuttering severity was associated with lower GM volume than less severe stuttering. Additionally, other studies have reported reduced functional connectivity between the IFG and left motor regions, and reduced FA in the left (and right posterior) IFG in stuttering Lu et al., 2009;Watkins et al., 2008). In contrast to these reports of left IFG anomalies, other investigations have reported increased or no GM differences in the left IFG in AWS compared to normally fluent adults (Beal et al., 2007;Jä ncke et al., 2004;Lu et al., 2010). ...
Article
Unlabelled: Multiple studies have reported both functional and neuroanatomical differences between adults who stutter and their normally fluent peers. However, the reasons for these differences remain unclear although some developmental data suggest that structural brain differences may be present in school-age children who stutter. In the present study, the corpus callosum of children with persistent stuttering, children who recovered from stuttering and typically developing children between 9 and 12 years of age was compared to test if the presence of aberrant callosal morphology is implicated in this disorder. The total corpus callosum midsagittal area and area of each subsection consisting of the rostrum, anterior midbody, posterior midbody and splenium were measured using MIPAV (Medical Image Processing, Analysis, and Visualization). Voxel-based morphometry (VBM) was also used to compare white matter volume. No differences were detected in the corpus callosum area or white matter volume between children with persistent stuttering, children who recovered from stuttering and typically developing children. These results agree with dichotic listening studies that indicate children who stutter show the typical right ear advantage. Therefore, the neural reorganization across the midline shown in adults who stutter may be the result of long-term adaptations to persistent stuttering. Learning outcomes: Educational objectives: After reading this article, the reader will be able to: (1) summarize research findings on corpus callosum development; and (2) discuss the characteristics of corpus callosum anatomy in stuttering.
... Indeed, as mentioned previously, speech fluency training increases cerebellar activity during reading and alters resting state cerebellar connectivity (De Nil et al., 2001;Lu et al., 2012). In stuttering, the cerebellum is typically more active during speech and is more connected with cortical networks (Lu et al., 2009(Lu et al., , 2010. The cerebellum could compensate for diminished connections between cortical speech regions by increasing attention-driven monitoring of speech output (Allen et al., 1997;Craig-McQuaide et al., 2014), which aligns with the repeated finding of hyperactive cerebellum in stuttering (Brown et al., 2005) and with the DIVA model of speech production (Guenther et al., 2006;Civier et al., 2010;Tourville and Guenther, 2011). ...
Article
Full-text available
Persistent developmental stuttering is characterized by speech production disfluency and affects 1% of adults. The degree of impairment varies widely across individuals and the neural mechanisms underlying the disorder and this variability remain poorly understood. Here, we elucidate compensatory mechanisms related to this variability in impairment using whole-brain functional and white matter connectivity analyses in persistent developmental stuttering. We found that people who stutter had stronger functional connectivity between cerebellum and thalamus than people with fluent speech, while stutterers with the least severe symptoms had greater functional connectivity between left cerebellum and left orbitofrontal cortex. Additionally, people who stutter had decreased functional and white matter connectivity among the perisylvian auditory, motor, and speech planning regions compared to typical speakers, but greater functional connectivity between the right basal ganglia and bilateral temporal auditory regions. Structurally, disfluency ratings were negatively correlated with white matter connections to left perisylvian regions and to the brain stem. Overall, we found increased connectivity among subcortical and reward network structures in people who stutter compared to controls. These connections were negatively correlated with stuttering severity, suggesting the involvement of cerebellum and orbitofrontal cortex may underlie successful compensatory mechanisms by more fluent stutterers.
... The recent explanatory models of DS, largely derived from the functional neuroimaging research, have unambiguously recognized the role of cortico-subcortical network in fluent speech production (Lu et al., 2009). Specifically, Alm (2004) proposed two types of timing cues (internal & external) that engage basal ganglia-pre-supplementary cortex and cerebellar-premotor cortex, respectively. ...
Article
The neural underpinnings of acquired neurogenic stuttering (ANS) remain largely speculative owing to the multitude of etiologies and cerebral substrates implicated with this fluency disorder. Systematic investigations of ANS under various fluency-enhancing conditions have begun only in the recent past and these studies are indicative of the heterogeneous nature of the disorder. In this context, we present the case of a subject with ANS who exhibited marked reduction in dysfluencies under masked auditory feedback (MAF), singing, and pacing (speech therapy). However, the adaptation effect was absent in our subject. By explaining these features in the light of recent explanatory hypotheses derived from developmental stuttering (DS), we highlight on the possible similarity in the neural underpinnings of ANS and DS.
... A number of more recent neuroimaging studies have also reported abnormal striatal activations or abnormal connections to/from striatal areas in AWS (e.g. Chang, Kenney, Loucks, & Ludlow, 2009;Chang & Zhu, 2013;Giraud et al., 2008;Lu et al., 2009). ...
Article
Full-text available
The cause of stuttering has many theoretical explanations. A number of research groups have suggested changes in the volume and/or function of the striatum as a causal agent. Two recent studies in children and one in adults who stutter (AWS) report differences in striatal volume compared that seen in controls; however, the laterality and nature of this anatomical volume difference is not consistent across studies. The current study investigated whether a reduction in striatal grey matter volume, comparable to that seen in children who stutter (CWS), would be found in AWS. Such a finding would support claims that an anatomical striatal anomaly plays a causal role in stuttering. We used voxel-based morphometry to examine the structure of the striatum in a group of AWS and compared it to that in a group of matched adult control subjects. Results showed a statistically significant group difference for the left caudate nucleus, with smaller mean volume in the group of AWS. The caudate nucleus, one of three main structures within the striatum, is thought to be critical for the planning and modulation of movement sequencing. The difference in striatal volume found here aligns with theoretical accounts of stuttering, which suggest it is a motor control disorder that arises from deficient articulatory movement selection and sequencing. Whilst the current study provides further evidence of a striatal volume difference in stuttering at the group level compared to controls, the significant overlap between AWS and controls suggests this difference is unlikely to be diagnostic of stuttering.
... To gain a better understanding of the impact of the BECTS syndrome on language processing in Chinese children, we sought to examine functional connectivity in children with BECTS and in healthy controls. An overt picture-naming task was used, which has been widely used to examine the neural correlates of speech production in healthy controls [17] and clinical populations [18]. We hypothesized that Chinese children with benign childhood epilepsy with centrotemporal spikes would show atypical functional connectivity in the brain regions associated with Chinese speech production. ...
Article
Previous studies have demonstrated that language impairments are frequently observed in patients with benign epilepsy with centrotemporal spikes (BECTS). However, how BECTS affects language processing in the Chinese population remains unclear. With the use of functional magnetic resonance imaging (fMRI) in an overt picture-naming task, the present study examined functional connectivity in 27 children with BECTS and 26 healthy controls. The results indicated that children with BECTS showed altered functional connectivity associated with speech production between the left precuneus and the right cerebellum, between the right precuneus and the bilateral thalamus and the left superior temporal gyrus, between the right cuneus and the right postcentral gyrus and the right inferior parietal lobule, and between the right cerebellum and right middle frontal gyrus. Collectively, the findings in this study demonstrate the abnormal functional connectivity basis of speech production in Chinese children with BECTS, providing clues to understanding the brain mechanisms of language-related network in patients with BECTS.
... The cerebellum is another critical hub area of the brain (Akkal et al. 2007;Bostan et al. 2010Bostan et al. , 2013Brodal 1978;Glickstein et al. 1985;Hoover and Strick 1999;Hoshi et al. 2005;Strick 2000, 2003;Leichnetz et al. 1984;Strick 1994, 2001;Schmahmann and Pandya 1991, 1997Snider and Maiti 1976;Strick et al. 2009;Tourville and Guenther 2011;Vilensky and Van Hoesen 1981;Zemanick et al. 1991). Arguably, the cerebellum has received much less exploration than other hub areas such as the basal ganglia, though a number of studies have reported cerebellar functional and structural differences in people who stutter (Beal et al. 2007;Brown et al. 2005;Budde et al. 2014;Chang et al. 2015;Chang et al. 2008Chang et al. , 2016Chang and Zhu 2013;Chow and Chang 2017;Connally et al. 2014;De Nil et al. 2001;Garnett et al. 2018;Kell et al. 2018;Lu et al. 2009Lu et al. , 2010aLu et al. , b, 2012Sitek et al. 2016;Song et al. 2007;Watkins et al. 2007;Yang et al. 2016). ...
Article
Full-text available
Cerebellar-cortical loops comprise critical neural circuitry that supports self-initiated movements and motor adjustments in response to perceived errors, functions that are affected in stuttering. It is unknown whether structural aspects of cerebellar circuitry are affected in stuttering, particularly in children close to symptom onset. Here we examined white matter diffusivity characteristics of the three cerebellar peduncles (CPs) based on diffusion MRI (dMRI) data collected from 41 children who stutter (CWS) and 42 controls in the 3–11 years range. We hypothesized that CWS would exhibit decreased fractional anisotropy (FA) in the right CPs given the contralateral connectivity of the cerebellar-cortical loops and past reports of structural differences in left cortical areas in stuttering speakers. Automatic Fiber Quantification (AFQ) was used to track and segment cerebellar white matter pathways and to extract diffusivity measures. We found significant group differences for FA in the right inferior CP (ICP) only: controls showed significantly higher FA in the right ventral ICP compared to CWS, controlling for age, sex, and verbal IQ. Furthermore, FA of right ICP was negatively correlated with stuttering frequency in CWS. These results suggest an early developmental difference in the right ICP for CWS compared to age-matched peers, which may indicate an alteration in error processing, a function previously linked to the ICP. Lower FA here may impact error monitoring and sensory input processing to guide motor corrections. Further longitudinal investigations in children may provide additional insights into how CP development links to stuttering persistence and recovery.
... Our findings reproduce significant group differences in the left MCP, demonstrating lower FA along a vast majority of nodes along this tract in AWS compared to fluent speakers (Connally et al., 2014). A recent tractography study in healthy human subjects showed that the MCP connects the cerebellum with the contralateral prefrontal and temporal cortices, including the SMA and IFG (Palesi et al., 2017), all of which have been implicated in stuttering (Brown et al., 2005;Cai et al., 2014;Chang et al., 2008Chang et al., , 2011Chang et al., , 2015De Nil et al., 2003;Kell et al., 2009;Lu et al., 2009Lu et al., , 2010Watkins et al., 2008). Here, we extend these findings by showing that the white matter fibers connecting the SMA and IFG with the cerebellum have different properties in AWS compared to fluent speakers. ...
Article
Introduction Individuals with persistent developmental stuttering display deficits in aligning motor actions to external cues (i.e., sensorimotor synchronization). Diffusion imaging studies point to stuttering-associated differences in dorsal, not ventral, white matter pathways, and in the cerebellar peduncles. Here, we studied microstructural white matter differences between adults who stutter (AWS) and fluent speakers using two complementary approaches to: (a) assess previously reported group differences in white matter diffusivity, and (b) evaluate the relationship between white matter diffusivity and sensorimotor synchronization in each group. Methods Participants completed a sensorimotor synchronization task and a diffusion MRI scan. We identified the cerebellar peduncles and major dorsal- and ventral-stream language pathways in each individual and assessed correlations between sensorimotor synchronization and diffusion measures along the tracts. Results The results demonstrated group differences in dorsal, not ventral, language tracts, in alignment with prior reports. Specifically, AWS had significantly lower fractional anisotropy (FA) in the left arcuate fasciculus, and significantly higher mean diffusivity (MD) in the bilateral frontal aslant tract compared to fluent speakers, while no significant group difference was detected in the inferior fronto-occipital fasciculus. We also found significant group differences in both FA and MD of the left middle cerebellar peduncle. Comparing patterns of association with sensorimotor synchronization revealed a novel double dissociation: MD within the left inferior cerebellar peduncle was significantly correlated with mean asynchrony in AWS but not in fluent speakers, while FA within the left arcuate fasciculus was significantly correlated with mean asynchrony in fluent speakers, but not in AWS. Conclusions Our results support the view that stuttering involves altered connectivity in dorsal tracts and that AWS may rely more heavily on cerebellar tracts to process timing information. Evaluating microstructural associations with sensitive behavioral measures provides a powerful tool for discovering additional functional differences in the underlying connectivity in AWS.
... It consisted of 46 channels located between the sources and detectors covering parts of the frontal, motor, parietal, and temporal cortices. Regions of interest were selected based on the results of six published research reports that used fMRI to examine speech production in AWS [16,51,50,56,61,72]. Fig. 2 shows the probe geometry. ...
Article
Few studies have investigated the neural mechanisms underlying speech production in children who stutter (CWS), despite the critical importance of understanding these mechanisms closer to the time of stuttering onset. The relative contributions of speech planning and execution in CWS therefore are also unknown. Using functional near-infrared spectroscopy, the current study investigated neural mechanisms of planning and execution in a small sample of 9–12 year-old CWS and controls (N = 12) by implementing two tasks that manipulated speech planning and execution loads. Planning was associated with atypical activation in bilateral inferior frontal gyrus and right supramarginal gyrus. Execution was associated with atypical activation in bilateral precentral gyrus and inferior frontal gyrus, as well as right supramarginal gyrus and superior temporal gyrus. The CWS exhibited some activation patterns that were similar to the adults who stutter (AWS) as reported in our previous study: atypical planning in frontal areas including left inferior frontal gyrus and atypical execution in fronto-temporo-parietal regions including left precentral gyrus, and right inferior frontal, superior temporal, and supramarginal gyri. However, differences also emerged. Whereas CWS and AWS both appear to exhibit atypical activation in right inferior and supramarginal gyri during execution, only CWS appear to exhibit this same pattern during planning. In addition, the CWS appear to exhibit atypical activation in left inferior frontal and right precentral gyri related to execution, whereas AWS do not. These preliminary results are discussed in the context of possible impairments in sensorimotor integration and inhibitory control for CWS.
... Recent findings from neuroimaging and genetic studies on stuttering have advanced our understanding of the neurological and cellular bases of the disorder Frigerio-Domingues & Drayna, 2017). Gross brain abnormalities a The Institute for Biomedical Sciences, School of Medicine and Health Sciences, The George Washington University, Washington, DC are not typically found in people who stutter, but subtle differences between people who stutter and their fluent peers have been found in gray matter volume (GMV; Beal et al., 2013;Chang et al., 2008;Chow et al., 2020), cortical thickness Whitaker et al., 2016), white matter diffusivity (Chow & Chang, 2017;Neef et al., 2015), metabolic rate (Wu et al., 1995), concentration of brain metabolites (O'Neill et al., 2017), brain activation during speech production (Braun et al., 1997;Fox et al., 1996), and functional magnetic resonance imaging (fMRI)-based functional connectivity Lu et al., 2009). In terms of genetic studies, genetic variations in four genes-GNPTAB, GNPTG, NAGPA, and AP4E1-have been identified to be associated with stuttering (Kang et al., 2010;Raza et al., 2015). ...
Article
Purpose The biological mechanisms underlying developmental stuttering remain unclear. In a previous investigation, we showed that there is significant spatial correspondence between regional gray matter structural anomalies and the expression of genes linked to energy metabolism. In the current study, we sought to further examine the relationship between structural anomalies in the brain in children with persistent stuttering and brain regional energy metabolism. Method High-resolution structural MRI scans were acquired from 26 persistent stuttering and 44 typically developing children. Voxel-based morphometry was used to quantify the between-group gray matter volume (GMV) differences across the whole brain. Group differences in GMV were then compared with published values for the pattern of glucose metabolism measured via F ¹⁸ fluorodeoxyglucose uptake in the brains of 29 healthy volunteers using positron emission tomography. Results A significant positive correlation between GMV differences and F ¹⁸ fluorodeoxyglucose uptake was found in the left hemisphere (ρ = .36, p < .01), where speech-motor and language processing are typically localized. No such correlation was observed in the right hemisphere (ρ = .05, p = .70). Conclusions Corroborating our previous gene expression studies, the results of the current study suggest a potential connection between energy metabolism and stuttering. Brain regions with high energy utilization may be particularly vulnerable to anatomical changes associated with stuttering. Such changes may be further exacerbated when there are sharp increases in brain energy utilization, which coincides with the developmental period of rapid speech/language acquisition and the onset of stuttering during childhood. Supplemental Material https://doi.org/10.23641/asha.14110454
... Along these lines, cerebellar differences were detected in several studies comparing people who stutter and fluent speakers using functional and structural imaging methods. For example, functional studies report elevated cerebellar activity in AWS (De Nil et al. 2003), an abnormal integration of information across the cerebellum-premotor circuit of AWS (Lu et al. 2009), and a positive correlation between speech rate and cerebellar activity among AWS (Fox et al. 2000). With respect to the cerebellar white matter structure, decreased fractional anisotropy values were found in both children who stutter (Chang et al. 2015) and AWS (Connally et al. 2014). ...
Article
Full-text available
Speech rate is a basic characteristic of language production, which affects the speaker’s intelligibility and communication efficiency. Various speech disorders, including persistent developmental stuttering, present altered speech rate. Specifically, adults who stutter (AWS) typically exhibit a slower speech rate compared to fluent speakers. Evidence from imaging studies suggests that the cerebellum contributes to the paced production of speech. People who stutter show structural and functional abnormalities in the cerebellum. However, the involvement of the cerebellar pathways in controlling speech rate remains unexplored. Here, we assess the association of the cerebellar peduncles with speech rate in AWS and control speakers. Diffusion MRI and speech-rate data were collected in 42 participants (23 AWS, 19 controls). We used deterministic tractography with Automatic Fiber segmentation and Quantification (AFQ) to identify the superior, middle, and inferior cerebellar peduncles (SCP, MCP, ICP) bilaterally, and quantified fractional anisotropy (FA) and mean diffusivity (MD) along each tract. No significant differences were observed between AWS and controls in the diffusivity values of the cerebellar peduncles. However, AWS demonstrated a significant negative association between speech rate and FA within the left ICP, a major cerebellar pathway that transmits sensory feedback signals from the olivary nucleus into the cerebellum. The involvement of the ICP in controlling speech production in AWS is compatible with the view that stuttering stems from hyperactive speech monitoring, where even minor deviations from the speech plan are considered as errors. In conclusion, our findings suggest a plausible neural mechanism for speech rate reduction observed in AWS.
... However, there is also evidence that neural differences in individuals who stutter may go beyond levels of activity in specific brain regions, additionally affecting connectivity between brain regions. Recent resting-state connectivity analyses suggest atypical functional brain organization in stuttering (Lu et al., 2009(Lu et al., , 2010Xuan et al., 2012;Chang et al., 2018), and white matter structure also seems to be affected (Jäncke et al., 2004;Watkins et al., 2008;Blecher et al., 2016;Kemerdere et al., 2016;Kronfeld-Duenias et al., 2016). Functional MRI analysis techniques like independent component analysis (ICA) can identify brain ''networks'' from fMRI data without resorting to seed regions or other a priori hypotheses. ...
Article
Full-text available
Stuttering is a disorder that impacts the smooth flow of speech production and is associated with a deficit in sensorimotor integration. In a previous experiment, individuals who stutter were able to vocally compensate for pitch shifts in their auditory feedback, but they exhibited more variability in the timing of their corrective responses. In the current study, we focused on the neural correlates of the task using functional MRI. Participants produced a vowel sound in the scanner while hearing their own voice in real time through headphones. On some trials, the audio was shifted up or down in pitch, eliciting a corrective vocal response. Contrasting pitch-shifted vs. unshifted trials revealed bilateral superior temporal activation over all the participants. However, the groups differed in the activation of middle temporal gyrus and superior frontal gyrus [Brodmann area 10 (BA 10)], with individuals who stutter displaying deactivation while controls displayed activation. In addition to the standard univariate general linear modeling approach, we employed a data-driven technique (independent component analysis, or ICA) to separate task activity into functional networks. Among the networks most correlated with the experimental time course, there was a combined auditory-motor network in controls, but the two networks remained separable for individuals who stuttered. The decoupling of these networks may account for temporal variability in pitch compensation reported in our previous work, and supports the idea that neural network coherence is disturbed in the stuttering brain.
... Although the studies reviewed herein provide broad support for basal ganglia-thalamocortical loop involvement in PDS, it is noteworthy that differences between fluent and stuttering individuals have been found for neural structures not in this loop, most notably the cerebellum (e.g., Connally et al., 2014;Yang et al., 2016), including numerous studies suggesting cerebellum-related mechanisms in compensation for stuttering (Lu et al., 2009;Etchell et al., 2014;Toyomura et al., 2015;Sitek et al., 2016;Kell et al., 2018). Importantly, the cerebellum and basal ganglia are interconnected at the subcortical level, with cerebellar output nuclei projecting to the striatum through a dense disynaptic projection (Bostan and Strick, 2018), suggesting the possibility that cerebellar projections to basal ganglia and/ or cerebral cortex may provide a means for compensating for impaired basal ganglia function in stuttering. ...
Article
Full-text available
Stuttering is a complex neurodevelopmental disorder that has to date eluded a clear explication of its pathophysiological bases. In this review, we utilize the Directions Into Velocities of Articulators (DIVA) neurocomputational modeling framework to mechanistically interpret relevant findings from the behavioral and neurological literatures on stuttering. Within this theoretical framework, we propose that the primary impairment underlying stuttering behavior is malfunction in the cortico-basal ganglia-thalamocortical (hereafter, cortico-BG) loop that is responsible for initiating speech motor programs. This theoretical perspective predicts three possible loci of impaired neural processing within the cortico-BG loop that could lead to stuttering behaviors: impairment within the basal ganglia proper; impairment of axonal projections between cerebral cortex, basal ganglia, and thalamus; and impairment in cortical processing. These theoretical perspectives are presented in detail, followed by a review of empirical data that make reference to these three possibilities. We also highlight any differences that are present in the literature based on examining adults versus children, which give important insights into potential core deficits associated with stuttering versus compensatory changes that occur in the brain as a result of having stuttered for many years in the case of adults who stutter. We conclude with outstanding questions in the field and promising areas for future studies that have the potential to further advance mechanistic understanding of neural deficits underlying persistent developmental stuttering.
... The SMA is critical in planning complex movement routines, including those that are required for fluent speech production, that are internally timed and initiated, rather than in response to external cues (Cunnington et al., 1996;Packman et al., 2007). PWS demonstrate difficulty in preparing and controlling precisely-timed complex movements including speech, poor performance on non-speech behavioral tasks that involve timing and rhythm and attenuated functional connectivity among BGTC regions (Packman and Onslow, 2002;Packman et al., 2007;Lu et al., 2009Lu et al., , 2010Chang and Zhu, 2013;Wieland et al., 2015;Chang et al., 2016). Interestingly, most PWS exhibit temporarily increased fluency during externally paced conditions such as choral speech or metronome-paced speech (Park and Logan, 2015). ...
Article
Full-text available
Stuttering is a neurodevelopmental disorder that manifests as frequent disruptions in the flow of speech, affecting 1% of adults. Treatments are limited to behavioral interventions with variable success and high relapse rates, particularly in adults. However, even in severe cases, fluency can be temporarily induced during conditions in which the speaker synchronizes his speech with external rhythmic cues, such as when reading in unison (choral speech) or with a metronome. Non-invasive neuromodulation techniques such as transcranial direct current stimulation (tDCS) have shown promise in augmenting the effects of behavioral treatment during motor and speech/language rehabilitation, but only one study to date has examined behavioral modulatory effects of tDCS in the context of stuttering. Using high-definition (HD)-tDCS electrodes, which improves focality of stimulation relative to conventional tDCS, we investigated the effects of tDCS on speech fluency and brain activation in 14 adults who stutter (AWS). Either anodal or sham stimulation was delivered on separate days over left supplementary motor area (SMA). During stimulation, participants read aloud in sync with a metronome. Measures of speech fluency and brain activity functional magnetic resonance imaging (fMRI) were collected before and after stimulation. No significant differences in brain activity or speech fluency were found when comparing active and sham stimulation. However, stuttering severity significantly modulated the effect of stimulation: active stimulation attenuated the atypically strong association between stuttering severity and right thalamocortical network activity, especially in more severe speakers. These preliminary results warrant additional research into potential application of HD-tDCS to modulate speech motor networks to enhance fluency in stuttering.
... With the advent of neuroimaging techniques, a paradigm shift arose implicating neuroanatomical factors and brain connectomic findings (Chang et al., 2015;Cieslak et al., 2015;De Nil et al., 2001;Wells and Moore, 1990;Brown et al., 2005). For instance, stuttering has been consistently associated with gray matter changes in the supplementary motor area (SMA), the primary motor area, the inferior frontal gyri, the pars opercularis (Brodmann area [BA] 44), the classical Broca and Wernicke areas, the superior temporal gyri, the subcentral area (BA 43), the insula, the precuneus, the basal ganglia-thalamo-cortical loop, the cerebellum and has more recently been associated with the default mode network, as well as changes in axonal tracts innervating motor, J o u r n a l P r e -p r o o f auditory and perisylvian areas of the frontal and parietal lobes (Braun et al., 1997;Chang et al., 2015Chang and Zhu, 2013;Fox, 2000;Fox et al., 1996;Ingham et al., 2012;Jiang et al., 2012;Lu et al., 2010Lu et al., , 2009Neef et al., 2018;Neumann et al., 2005;Sakai et al., 2009;Wu et al., 1995). More recently, research has focused on a novel interpretation of this speech condition: the genetic foundations of stuttering (Drayna and Kang, 2011;Kang et al., 2010;Raza et al., 2016). ...
Article
The neurobiological underpinnings of stuttering, a speech disorder characterized by disrupted speech fluency, remain unclear. While recent developments in the field have afforded researchers with the ability to pinpoint several genetic profiles associated with stuttering, how these specific genetic backgrounds impact neuronal circuits and how they generate or facilitate the emergence of stuttered speech remains unknown. In this study we identified the large-scale cortical network that characterizes stuttering using functional connectivity MRI and graph theory. We performed a spatial similarity analysis that examines whether the topology of the stuttering cortical network intersects with genetic expression levels of previously reported genes for stuttering from the protein-coding transcriptome data of the Allen Human Brain Atlas. We found that GNPTG – a gene involved in the mannose-6-phosphate lysosomal targeting pathways – was significantly co-localized with the stuttering cortical network. An enrichment analysis demonstrated that the genes identified with the stuttering cortical network shared a significantly overrepresented biological functionality of Neurofilament Cytoskeleton Organization (NEFH, NEFL and INA). The relationship between lysosomal pathways, cytoskeleton organization, and stuttering, was investigated by comparing the genetic interactome between GNPTG and the neurofilament genes implicated in the current study. We found that genes of the interactome network, including CDK5, SNCA, and ACTB, act as functional links between lysosomal and neurofilament genes. These findings support stuttering is due to a lysosomal dysfunction that impart deleterious effects on the neurofilament organization of the speech neuronal circuits. They help in solving the intriguing unsolved link between lysosomal mutations and the presence of stuttering.
... These notions are supported by several lines of empirical evidence. Some studies reported that PWS have difficulties in speech planning during covert and overt speech production (Chang et al., 2009;Lu et al., 2009;Lu et al., 2010), while other studies demonstrated the phonological perception deficit in PWS (Lu et al., 2016;Pelczarski & Yaruss, 2014). ...
Article
Persistent developmental stuttering is a neurological disorder that commonly manifests as a motor problem. Cognitive theories, however, hold that poorly developed cognitive skills are the origins of stuttering. Working memory (WM), a multicomponent cognitive system that mediates information maintenance and manipulation, is known to play an important role in speech production, leading us to postulate that the neurophysiological mechanisms underlying stuttering may be associated with a WM deficit. Using functional magnetic resonance imaging, we aimed to elucidate brain mechanisms in a phonological WM task in adults who stutter and controls. A right‐lateralized compensatory mechanism for a deficit in the rehearsal process and neural disconnections associated with the central executive dysfunction were found. Furthermore, the neural abnormalities underlying the phonological WM were independent of memory load. This study demonstrates for the first time the atypical neural responses to phonological WM in PWS, shedding new light on the underlying cause of stuttering.
... Results from this body of work are mixed. Some studies report that both children and adults who stutter exhibit aberrant auditory-motor integration (Beal et al., 2010(Beal et al., , 2011Chang & Zhu, 2013;Jansson-Verkasalo et al., 2014) and possible deficiencies in the basal-ganglia thalamocortical loop (Lu et al., 2009(Lu et al., , 2010Chang & Zhu, 2013;Xuan et al., 2012), whereas others provide conflicting findings (e.g., right hemisphere increases in structural measures) in adults (De Nil, Kroll, Kapur, & Houle, 2000;Foundas et al., 2003;Kikuchi, Ogata, & Umesaki, 2011;Preibisch et al., 2003) but not in children (Chang et al., 2008) and an absence of differences in lateralization of brain function during speech production in children who stutter (Sowman et al., 2014). Convergent findings from children and adults have been considered to reflect stuttering trait-associated differences in the brain that may be related to pathophysiology of stuttering. ...
Article
Purpose: We combined a large longitudinal neuroimaging dataset that includes children who do and do not stutter and a whole-brain network analysis in order to examine the intra- and inter-network connectivity changes associated with stuttering. Additionally, we asked whether whole brain connectivity patterns observed at the initial year of scanning could predict persistent stuttering in later years. Methods: A total of 224 high-quality resting state fMRI scans collected from 84 children (42 stuttering, 42 controls) were entered into an independent component analysis (ICA), yielding a number of distinct network connectivity maps ("components") as well as expression scores for each component that quantified the degree to which it is expressed for each child. These expression scores were compared between stuttering and control groups' first scans. In a second analysis, we examined whether the components that were most predictive of stuttering status also predicted persistence in stuttering. Results: Stuttering status, as well as stuttering persistence, were associated with aberrant network connectivity involving the default mode network and its connectivity with attention, somatomotor, and frontoparietal networks. The results suggest developmental alterations in the balance of integration and segregation of large-scale neural networks that support proficient task performance including fluent speech motor control. Conclusions: This study supports the view that stuttering is a complex neurodevelopmental disorder and provides comprehensive brain network maps that substantiate past theories emphasizing the importance of considering situational, emotional, attentional and linguistic factors in explaining the basis for stuttering onset, persistence, and recovery.
Preprint
Stuttering is a complex neurodevelopmental disorder that has to date eluded a clear explication of its pathophysiological bases. In this review, we utilize the Directions Into Velocities of Articulators (DIVA) neurocomputational modeling framework to mechanistically interpret relevant findings from the behavioral and neurological literatures on stuttering. Within this theoretical framework, we propose that the primary impairment underlying stuttering behavior is malfunction in the cortico-basal ganglia-thalamocortical (hereafter, cortico-BG) loop that is responsible for initiating speech motor programs. This theoretical perspective predicts three possible loci of impaired neural processing within the cortico-BG loop that could lead to stuttering behaviors: impairment within the basal ganglia proper, impairment of axonal projections between cerebral cortex, basal ganglia, and thalamus, and impairment in cortical processing. These theoretical perspectives are presented in detail, followed by a review of empirical data that make reference to these three possibilities. We also highlight any differences that are present in the literature based on examining adults versus children, which give important insights into potential core deficits associated with stuttering versus compensatory changes that occur in the brain as a result of having stuttered for many years in the case of adults who stutter. We conclude with outstanding questions in the field and promising areas for future studies that have the potential to further advance mechanistic understanding of neural deficits underlying persistent developmental stuttering.
Article
Full-text available
Stuttering occurs in approximately 5% of all children and 1% of adults. One type, neurogenic stuttering, is usually attributable to strokes or other structural damages to the brain areas that are responsible for language fluency. Here, we present the first case of neurogenic stuttering caused by a brain abscess. The patient was a 60-year-old man admitted for a seizure and administered an anticonvulsant, after which he began stuttering. MRI revealed a brain abscess in the left frontal lobe that extended to the dorsolateral prefrontal cortex (BA (Brodmann’s area) 9 and 46), frontal eye field (BA 8) and premotor cortex and supplementary motor area (BA 6). After neurosurgical drainage and antibiotic treatment, the symptoms had resolved. This case is unique in that the therapeutic effects and localisation of the cause of stuttering were rapidly identified, allowing for a more accurate description of the neural circuitry related to stuttering.
Article
The neural mechanisms underlying stuttering are not well understood. It is known that stuttering appears when persons who stutter speak in a self-paced manner, but speech fluency is temporarily increased when they speak in unison with external trigger such as a metronome. This phenomenon is very similar to the behavioral improvement by external pacing in patients with Parkinson's disease. Recent imaging studies have also suggested that the basal ganglia is involved in the etiology of stuttering. In addition, previous studies have shown that the basal ganglia is involved in self-paced movement. Then, the present study focused on the basal ganglia and explored whether long-term speech-practice using external triggers can induce modification of the basal ganglia activity of stuttering speakers. Our study of functional magnetic resonance imaging revealed that stuttering speakers possessed significantly lower activity in the basal ganglia than fluent speakers before practice, especially when their speech was self-paced. After an 8-week speech practice of externally triggered speech using a metronome, the significant difference in activity between the two groups disappeared. The cerebellar vermis of stuttering speakers showed significantly decreased activity during the self-paced speech in the second compared to the first experiment. The speech fluency and naturalness of the stuttering speakers were also improved. These results suggest that stuttering is associated with defective motor control during self-paced speech, and that the basal ganglia and the cerebellum are involved in an improvement of speech fluency of stuttering by the use of external trigger. Copyright © 2015 Elsevier Inc. All rights reserved.
Article
The ability to express thoughts through fluent speech production is a most human faculty, one that is often taken for granted. Stuttering, which disrupts the smooth flow of speech, affects approximately 5% of preschool-age children and 1% of the general population, and can lead to significant communication difficulties and negative psychosocial consequences throughout one’s lifetime. Despite the fact that symptom onset typically occurs during early childhood, few studies have yet examined the possible neural bases of developmental stuttering during childhood. Here we present a diffusion tensor imaging study that examined white matter measures reflecting neuroanatomical connectivity (fractional anisotropy; FA) in 77 children (40 controls [20F], 37 who stutter [16F]) between 3-10 years of age. We asked whether previously reported anomalous white matter (WM) measures in adults and older children who stutter that were found primarily in major left hemisphere tracts (e.g., superior longitudinal fasciculus) are also present in younger children who stutter. All children exhibited normal speech, language, and cognitive development as assessed through a battery of assessments. The two groups were matched in chronological age and socioeconomic status. Voxel-wise whole brain comparisons using tract based spatial statistics (TBSS) and region of interest analyses of FA were conducted to examine white matter changes associated with stuttering status, age, sex, and stuttering severity. Children who stutter exhibited significantly reduced FA relative to controls in WM tracts that interconnect auditory and motor structures, corpus callosum, and in tracts interconnecting cortical and subcortical areas. In contrast to controls, FA changes with age were either stagnant or showed dissociated development among major brain areas in children who stutter. These results provide first glimpses into the neuroanatomical bases of early childhood stuttering, and possible white matter developmental changes that may lead to recovery versus chronic stuttering. The white matter changes point to possible structural connectivity deficits in children who stutter, in inter-related neural circuits that enable skilled movement control through efficient sensorimotor integration and timing of movements.
Preprint
Full-text available
Cerebellar-cortical loops comprise critical neural circuitry that supports self-initiated movements and motor adjustments in response to perceived errors, functions that are affected in stuttering. It is unknown whether structural aspects of cerebellar circuitry are affected in stuttering, in particular in children close to symptom onset. Here we examined white matter diffusivity characteristics of the three cerebellar peduncles (CP) based on diffusion MRI (dMRI) data collected from 41 children who stutter (CWS) and 42 controls in the 3-11 year range. We hypothesized that CWS would exhibit decreased fractional anisotropy (FA) in the right CPs given the contralateral connectivity of the cerebellar-cortical loops and past reports of structural differences in left cortical areas in stuttering speakers. Automatic Fiber Quantification (AFQ) was used to track and segment cerebellar white matter pathways and to extract diffusivity measures. We found significant group differences for FA in the right Inferior CP (ICP) only: controls showed significantly higher FA in the right ventral ICP compared to CWS, controlling for age, sex, and verbal IQ. Furthermore, FA of right ICP was negatively correlated with stuttering frequency in CWS. These results suggest an early developmental difference in the right ICP for CWS compared to age-matched peers, which may indicate an alteration in error processing, a function previously linked to the ICP. Lower FA here may impact error monitoring and sensory input processing to guide motor corrections. Further longitudinal investigations in children may provide additional insights into how CP development links to stuttering persistence and recovery.
Article
Here, we describe the development of a minimally supervised pipeline for the analysis of event-related magnetoencephalography (MEG) recordings that preserves the temporal resolution of the data and enables estimation of patterns of regional interdependencies between activated regions. The method was applied to MEG recordings obtained from six right-handed young adults performing an overt naming task using a whole-head system with 248 axial magnetometers. Minimum norm estimates of distributed source currents were calculated in Brainstorm during the first 400 ms post-stimulus onset. A spatiotemporal sourceclustering algorithm was applied to identify extended regions of significant activation as compared to the prestimulus baseline for each participant. Finally, regional interdependencies were estimated through crosslag correlation analysis between time-series representing the time course of activity within each cluster. Consistently across participants activation loci were found in primary and association visual cortices, the fusiform and lingual gyri, the posterior portion of the superior and middle temporal gyri (MTG), the anterior, middle-inferior temporal lobe (ITG), and the inferior (IFG) and middle frontal gyri (MFG). Regions where dynamic activation patterns appeared to be “affected” by prior activation in primary/ association visual cortices and the fusiform gyrus were found in the MTG/anterior ITG, and MFG. Immediately prior to articulation, activations were found in IFG, ITG, fusiform and supramarginal gyri.
Article
Speaking of stuttering as an audible phenomenon tells us little or nothing about the complexity and the dynamics of the neural structures during the manifestation of a stuttering moment. Speaking of stuttering tells us little about the differences that exist as well as at the level of audible symptoms as about the eventual causes of that precise stuttering moment. It is this complexity and these dynamics that are questioned in this article.
Article
Full-text available
People who stutter learn to anticipate many of their overt stuttering events. Despite the critical role of anticipation, particularly how responses to anticipation shape stuttering behaviors, the neural bases associated with anticipation are unknown. We used a novel approach to identify anticipated and unanticipated words in 22 adult stutterers, which were produced in a delayed-response task while hemodynamic activity was measured using functional near infrared spectroscopy (fNIRS). Twenty-two control participants were included such that each individualized set of anticipated/unanticipated words was produced by one stutterer and one control. We conducted an analysis on the right dorsolateral prefrontal cortex (R-DLPFC) based on converging lines of evidence from the stuttering and cognitive control literatures. We also assessed connectivity between the R-DLPFC and right supramarginal gyrus (R-SMG), two key nodes of the frontoparietal network (FPN), to assess the role of cognitive control, particularly error-likelihood monitoring, in stuttering anticipation. All analyses focused on the five-second anticipation phase preceding the go signal to produce speech. Results indicate that anticipated words are associated with elevated activation in the R-DLPFC, and that compared to non-stutterers, stutterers exhibit greater activity in the R-DLPFC, irrespective of anticipation. Further, anticipated words are associated with reduced connectivity between the R-DLPFC and R-SMG. These findings highlight the potential roles of the R-DLPFC and the greater FPN as a neural substrate of stuttering anticipation. The results also support previous accounts of error-likelihood monitoring and action-stopping in stuttering anticipation. Overall, this work offers numerous directions for future research with clinical implications for targeted neuromodulation.
Article
Persistent developmental stuttering is a neurologically based speech disorder associated with cognitive-linguistic, motor and emotional abnormalities. Previous studies investigating the relationship between anxiety and stuttering have yielded mixed results, but it has not yet been examined whether anxiety influences brain activity underlying stuttering. Here, by using functional magnetic resonance imaging (fMRI), we investigated the functional connectivity associated with state anxiety in a syllable repetition task, and trait anxiety during rest in adults who stutter (N=19) and fluent controls (N=19). During the speech task, people who stutter (PWS) showed increased functional connectivity of the right amygdala with the prefrontal gyrus (the left ventromedial frontal gyrus and right middle frontal gyrus) and the left insula compared to controls. During rest, PWS showed stronger functional connectivity between the right hippocampus and the left orbital frontal gyrus, and between the left hippocampus and left motor areas than controls. Taken together, our results suggest aberrant bottom-up and/or top-down interactions for anxiety regulation, which might be responsible for the higher level of state anxiety during speech and for the anxiety-prone trait in PWS. To our knowledge, this is the first study to examine the neural underpinnings of anxiety in PWS, thus yielding new insight in the causes of stuttering which might aid strategies for the diagnosis and treatment of stuttering.
Article
Full-text available
The analysis of brain imaging data has recently focused on the examination of the covariances of activity among neural regions during different behaviors. We present some of the theoretical and technical issues surrounding one of these covariance-based methods: structural equation modeling. In structural equation modeling, connections between brain areas are based on known neuroanatomy, and the interregional covariances of activity are used to calculate path coefficients representing the magnitude of the influence of each directional path. The logic behind the use of structural equation modeling stems from the suggestion that brain function is the result of changes in the covariances of activity among neural elements. The technical foundations for neural structural equation models are presented, emphasizing the ability to make inferential comparisons to evaluate the experimental changes in path coefficients. Simulated data sets were used to test the effects of omitted regions and omitted connections. The results suggested that structural modeling algorithms can give hints as to possible external influences and missing paths, but that the final decision as to model modifications requires the guidance of the researcher. The utility of anatomically based models to distinguish between the direct effect of one region on another, and indirect effects of darkness or patterned light on the metabolic activity in the rat visual system. The anatomical framework for the structural equation models revealed that the total impact of ascending thalamocortical influences was modified by corticocortical interactions. Extensions of structural equation modeling to human brain imaging experiments are presented. We conclude by suggesting that neural covariances may be a more accurate way to examine the dynamic functional organization of the central nervous system. ©1994 Wiley-Liss, Inc.
Article
Full-text available
We used functional magnetic resonance imaging to investigate the effect of two factors on the neural control of temporal sequence performance: the modality in which the rhythms had been trained, and the modality of the pacing stimuli preceding performance. The rhythms were trained 1-2 days before scanning. Each participant learned two rhythms: one was presented visually, the other auditorily. During fMRI, the rhythms were performed in blocks. In each block, four beats of a visual or auditory pacing metronome were followed by repetitive self-paced rhythm performance from memory. Data from the self-paced performance phase was analysed in a 2x2 factorial design, with the two factors Training Modality (auditory or visual) and Metronome Modality (auditory or visual), as well as with a conjunction analysis across all active conditions, to identify activations that were independent of both Training Modality and Metronome Modality. We found a significant main effect only for visual versus auditory Metronome Modality, in the left angular gyrus, due to a deactivation of this region after auditory pacing. The conjunction analysis revealed a set of brain areas that included dorsal auditory pathway areas (left temporo-parietal junction area and ventral premotor cortex), dorsal premotor cortex, the supplementary and presupplementary premotor areas, the cerebellum and the basal ganglia. We conclude that these regions are involved in controlling performance of well-learned rhythms, regardless of the modality in which the rhythms are trained and paced. This suggests that after extensive short-term training, all rhythms, even those that were both trained and paced in visual modality, had been transformed into auditory-motor representations. The deactivation of the angular cortex following auditory pacing may represent cross-modal auditory-visual inhibition.
Article
Full-text available
Brain metabolic mapping techniques, such as positron emission tomography (PET), can provide information about the functional interactions within entire neural systems. With the large quantity of data that can accumulate from a mapping study, a network analysis, which makes sense of the complex interactions among neural elements, is necessary. A network analysis was performed on data obtained from a PET study that examined both the changes in regional cerebral blood flow (rCBF) and interregional correlations among human cortical areas during performance of an object vision (face matching) and spatial vision (dot-location matching) task. Brain areas for the network were selected based on regions showing significant rCBF or interregional correlations between tasks. Anterior temporal and frontal lobe regions were added to the network using a principal components analysis. Interactions among selected regions were quantified with structural equation modeling. In the structural equation models, connections between brain areas were based on known neuroanatomy and the interregional correlations were used to calculate path coefficients representing the magnitude of the influence of each directional path. The combination of the anatomical network and interregional correlations created a functional network for each task. The functional network for the right hemisphere showed that in the object vision task, dominant path influences were among occipitotemporal areas, while in the spatial vision task, occipitoparietal interactions were stronger. The network for the spatial vision task also had a strong feedback path from area 46 to occipital cortex, an effect that was absent in the object vision task. There were strong interactions between dorsal and ventral pathways in both networks. Functional networks for the left hemisphere did not differ between tasks. Networks for the interhemispheric interactions showed that the dominant pathway in the right hemisphere also had stronger effects on homologous left hemisphere areas and are consistent with a hypothesis that intrahemispheric interactions were greater in the right hemisphere in both tasks, and that these influences were transmitted callosally to the left hemisphere.
Article
Full-text available
The cause of stuttering is unknown. Failure to develop left-hemispheric dominance for speech is a long-standing theory although others implicated the motor system more broadly, often postulating hyperactivity of the right (language nondominant) cerebral hemisphere. As knowledge of motor circuitry has advanced, theories of stuttering have become more anatomically specific, postulating hyperactivity of premotor cortex, either directly or through connectivity with the thalamus and basal ganglia. Alternative theories target the auditory and speech production systems. By contrasting stuttering with fluent speech using positron emission tomography combined with chorus reading to induce fluency, we found support for each of these hypotheses. Stuttering induced widespread overactivations of the motor system in both cerebrum and cerebellum, with right cerebral dominance. Stuttered reading lacked left-lateralized activations of the auditory system, which are thought to support the self-monitoring of speech, and selectively deactivated a frontal-temporal system implicated in speech production. Induced fluency decreased or eliminated the overactivity in most motor areas, and largely reversed the auditory-system underactivations and the deactivation of the speech production system. Thus stuttering is a disorder affecting the multiple neural systems used for speaking.
Article
Full-text available
This positron emission tomography study dissociates the neural correlates of object recognition and naming. Stimuli comprised coloured outline drawings of objects and coloured nonsense shapes. Subjects either viewed or explicitly named objects, similarly they viewed or named the colour of the shapes. Activations common to object and colour naming were identified by contrasting the explicit naming conditions (objects and colours) with the control (viewing) conditions. Activations associated with object recognition were identified by contrasting both object conditions (naming and viewing) with both shape conditions and activations specific to object or colour naming were identified by contrasting object naming (relative to object viewing) with colour naming (relative to shape viewing). The results associate: (i) object recognition with left middle occipital and bilateral anterior temporal cortices; (ii) modality independent naming with left posterior basal temporal lobe and the left prefrontal cortex; (iii) areas specific to object naming with left temporal extrasylvian regions, left anterior insula and right cerebellum; and (iv) areas specific to colour naming with left posterior lingual and fusiform gyri and midline cerebellum. These results are discussed in relation to previous neuroimaging and neuropsychological findings.
Article
Full-text available
Editor's introduction In longitudinal research we need computer programs to handle the complex statistical models necessary for the analysis of the longitudinal data. Based on the central features of the design of a longitudinal project, meaning that the same or similar measurements are obtained from the same people on two or more occasions, and in view of so-called "latent variables" as well as statistical covariance structure models, Karl G. JSreskog presents the LISREL computer program. LISREL will allow analysis of variables of any scale type.
Article
Full-text available
To assess dynamic brain function in adults who had stuttered since childhood, regional cerebral blood flow (rCBF) was measured with H2O and PET during a series of speech and language tasks designed to evoke or attenuate stuttering. Speech samples were acquired simultaneously and quantitatively compared with the PET images. Both hierarchical task contrasts and correlational analyses (rCBF versus weighted measures of dysfluency) were performed. rCBF patterns in stuttering subjects differed markedly during the formulation and expression of language, failing to demonstrate left hemispheric lateralization typically observed in controls; instead, regional responses were either absent, bilateral or lateralized to the right hemisphere. Significant differences were detected between groups when all subjects were fluent-during both language formulation and non-linguistic oral motor tasks-demonstrating that cerebral function may be fundamentally different in persons who stutter, even in the absence of stuttering. Comparison of scans acquired during fluency versus dysfluency-evoking tasks suggested that during the production of stuttered speech, anterior forebrain regions-which play an a role in the regulation of motor function-are disproportionately active in stuttering subjects, while post-rolandic regions-which play a role in perception and decoding of sensory information-are relatively silent. Comparison of scans acquired during these conditions in control subjects, which provide information about the sensorimotor or cognitive features of the language tasks themselves, suggest a mechanism by which fluency-evoking maneuvers might differentially affect activity in these anterior and posterior brain regions and may thus facilitate fluent speech production in individuals who stutter. Both correlational and contrast analyses suggest that right and left hemispheres play distinct and opposing roles in the generation of stuttering symptoms: activation of left hemispheric regions appears to be related to the production of stuttered speech, while activation of right hemispheric regions may represent compensatory processes associated with attenuation of stuttering symptoms.
Article
Full-text available
The perception and production of temporal patterns, or rhythms, is important for both music and speech. However, the way in which the human brain achieves accurate timing of perceptual input and motor output is as yet little understood. Central control of both motor timing and perceptual timing across modalities has been linked to both the cerebellum and the basal ganglia (BG). The present study was designed to test the hypothesized central control of temporal processing and to examine the roles of the cerebellum, BG, and sensory association areas. In this positron emission tomography (PET) activation paradigm, subjects reproduced rhythms of increasing temporal complexity that were presented separately in the auditory and visual modalities. The results provide support for a supramodal contribution of the lateral cerebellar cortex and cerebellar vermis to the production of a timed motor response, particularly when it is complex and/or novel. The results also give partial support to the involvement of BG structures in motor timing, although this may be more directly related to implementation of the motor response than to timing per se. Finally, sensory association areas and the ventrolateral frontal cortex were found to be involved in modality-specific encoding and retrieval of the temporal stimuli. Taken together, these results point to the participation of a number of neural structures in the production of a timed motor response from an external stimulus. The role of the cerebellum in timing is conceptualized not as a clock or counter but simply as the structure that provides the necessary circuitry for the sensory system to extract temporal information and for the motor system to learn to produce a precisely timed response.
Article
Full-text available
During learning, neural responses decrease over repeated exposure to identical stimuli. This repetition suppression is thought to reflect a progressive optimization of neuronal responses elicited by the task. Functional magnetic resonance imaging was used to study the neural basis of associative learning of visual objects and their locations. As expected, activation in specialized cortical areas decreased with time. However, with path analysis it was shown that, in parallel to this adaptation, increases in effective connectivity occurred between distinct cortical systems specialized for spatial and object processing. The time course of these plastic changes was highly correlated with individual learning performance, suggesting that interactions between brain areas underlie associative learning.
Article
The voice we most often hear is our own, and proper interaction between speaking and hearing is essential for both acquisition and performance of spoken language. Disturbed audiovocal interactions have been implicated in aphasia, stuttering, and schizophrenic voice hallucinations, but paradigms for a noninvasive assessment of auditory self-monitoring of speaking and its possible dysfunctions are rare. Using magnetoencephalograpy we show here that self-uttered syllables transiently activate the speaker's auditory cortex around 100 ms after voice onset. These phasic responses were delayed by 11 ms in the speech-dominant left hemisphere relative to the right, whereas during listening to a replay of the same utterances the response latencies were symmetric. Moreover, the auditory cortices did not react to rare vowel changes interspersed randomly within a series of repetitively spoken vowels, in contrast to regular change-related responses evoked 100–200 ms after replayed rare vowels. Thus, speaking primes the human auditory cortex at a millisecond time scale, dampening and delaying reactions to self-produced “expected” sounds, more prominently in the speech-dominant hemisphere. Such motor-to-sensory priming of early auditory cortex responses during voicing constitutes one element of speech self-monitoring that could be compromised in central speech disorders. Hum. Brain Mapping 9:183–191, 2000. © 2000 Wiley-Liss, Inc.
Article
To distinguish the neural systems of normal speech from those of stuttering, PET images of brain blood flow were probed (correlated voxel-wise) with per-trial speech-behaviour scores obtained during PET imaging. Two cohorts were studied: 10 right-handed men who stuttered and 10 right-handed, age- and sex-matched non-stuttering controls. Ninety PET blood flow images were obtained in each cohort (nine per subject as three trials of each of three conditions) from which r -value statistical parametric images (SPI{ r }) were computed. Brain correlates of stutter rate and syllable rate showed striking differences in both laterality and sign (i.e. positive or negative correlations). Stutter-rate correlates, both positive and negative, were strongly lateralized to the right cerebral and left cerebellar hemispheres. Syllable correlates in both cohorts were bilateral, with a bias towards the left cerebral and right cerebellar hemispheres, in keeping with the left-cerebral dominance for language and motor skills typical of right-handed subjects. For both stutters and syllables, the brain regions that were correlated positively were those of speech production: the mouth representation in the primary motor cortex; the supplementary motor area; the inferior lateral premotor cortex (Broca's area); the anterior insula; and the cerebellum. The principal difference between syllable-rate and stutter-rate positive correlates was hemispheric laterality. A notable exception to this rule was that cerebellar positive correlates for syllable rate were far more extensive in the stuttering cohort than in the control cohort, which suggests a specific role for the cerebellum in enabling fluent utterances in persons who stutter. Stutters were negatively correlated with right-cerebral regions (superior and middle temporal gyrus) associated with auditory perception and processing, regions which were positively correlated with syllables in both the stuttering and control cohorts. These findings support long-held theories that the brain correlates of stuttering are the speech-motor regions of the non-dominant (right) cerebral hemisphere, and extend this theory to include the non-dominant (left) cerebellar hemisphere. The present findings also indicate a specific role of the cerebellum in the fluent utterances of persons who stutter. Support is also offered for theories that implicate auditory processing problems in stuttering.
Article
We investigated whether posterior parietal cortex controls attentional switching when the tasks involve neither spatial nor visual cognition. Normal volunteers were scanned using functional MRI (fMRI). In all conditions, subjects were required to covertly produce words in verbal fluency tasks. They did so at a rate of one every 2 s (with eyes closed) in response to an auditory beep. In the non‐switching (NS) trials, subjects responded with a series of items from a prespecified semantic category (SC) (e.g. fruits or cars) and from overlearned sequences (OSs) (days of the week, months of the year or letters of the alphabet). Instructions as to which category items should be drawn from on a given run of trials were presented over fMRI‐compatible earphones prior to each run. In the switching (S) trials, subjects produced a series of word triads from three SCs: for example, fruits, cars and furniture (e.g. pear, Mercedes, table…); and from three OSs: days of the week, months of the year and letters of the alphabet (e.g. Monday, January, A…). This design is factorial, with the factors verbal class (SC or OSs) and switching conditions (S or NS). Increases in neural activity ( P < 0.05, corrected for multiple comparisons) were observed only in superior posterior parietal cortex bilaterally as a main effect of the S conditions compared with the NS conditions. When SC fluency was compared with OS fluency, significant activations were found in anterior cingulate cortex bilaterally, the left inferior frontal gyrus, the middle frontal gyrus bilaterally, frontal operculum bilaterally and in the cerebellar vermis. These results support the hypothesis that superior posterior parietal cortex is a supramodal area implicated in task switching, even when no visual or spatial component is implicated in the tasks. Task switching, frequently used to examine ‘frontal’ executive functions, may also be clinically relevant to the assessment of patients with superior posterior parietal lesions. Received May 23, 2001. Revised October 12, 2001. Second revision November 25, 2001. Accepted November 30, 2001
Article
A list of 144 words was presented to 15 school-age stutterers who were instructed to mark those words on which they would expect to be dysfluent if they were to readthem aloud. Subsequently, a computer-controlled eyemarker recorded the subjects' saccadic movements as they silently read a passage made up of these words. Then, they were videotaped as they orally read the passage.The childrens' expectations were not predictive of the words on which stuttering occured. Moreover, during silent reading, the subjects did not fixate more frequently on words subsequently stuttered than on those later spoken fluently. However, the duration of eye fixations during silent reading were longer for words that were subsequently stuttered than they were for those later spoken fluently. The latter finding suggest that school-aged children, like adults, show evidence of word-specific anticipation of dysfluency.
Article
By several accounts, reading single words may be accomplished either by sequentially transcribing orthographic units into their corresponding sounds (an indirect route), or by directly associating a visual word form to the semantic or articulatory representation (a direct route). By contrast, the similar task of naming objects must rely only on a direct route, since objects cannot be “sounded out.” To study the localization of cognitive processes specific to reading, we used positron emission tomography (PET) to measure regional cerebral blood flow while subjects named words and pictures of objects silently or aloud. Group averages of blood flow changes were obtained for experimental vs. control tasks. Object and word presentations elicited similar blood flow increases in extra‐striate visual cortices compared with a visual noise control. Silent reading invoked a neural network very similar to that seen when subjects named objects silently, consistent with a “direct” route. Naming objects aloud produced the addition of motor output regions to this network. By contrast, oral reading produced a markedly different pattern of activated regions, suggesting reliance on a separate phonological pathway. These results provide support for the dual coding hypothesis in reading and challenge the use of strict hierarchical models of cognitive operations in PET activation studies. © 1995 Wiley‐Liss, Inc.
Article
The typical functional magnetic resonance (fMRI) study presents a formidable problem of multiple statistical comparisons (i.e, > 10,000 in a 128 x 128 image). To protect against false positives, investigators have typically relied on decreasing the per pixel false positive probability. This approach incurs an inevitable loss of power to detect statistically significant activity. An alternative approach, which relies on the assumption that areas of true neural activity will tend to stimulate signal changes over contiguous pixels, is presented. If one knows the probability distribution of such cluster sizes as a function of per pixel false positive probability, one can use cluster-size thresholds independently to reject false positives. Both Monte Carlo simulations and fMRI studies of human subjects have been used to verify that this approach can improve statistical power by as much as fivefold over techniques that rely solely on adjusting per pixel false positive probabilities.
Article
Conventional t-statistics and cross-correlation coefficients are commonly used for analysis of functional magnetic resonance images. The sensitivity of these statistics is usually low because severe Bonferroni-type corrections are required for multiple statistical comparisons to minimize the false-positive error. In the human brain, most functional areas are larger in size than a single image pixel, and coactivation of numerous contiguous pixels is expected. The probability of occurrence of clusters due to random noise is small and can be modeled. Cluster size and intensity thresholding can be used to assess statistical significance. Previous cluster analysis strategies used Gaussian models, working best with low spatial resolution images (e.g., positron emission tomography). We present a new cluster analysis model applicable to data with little or even no covariance between adjacent pixels. Computer simulations and phantom experiments were used to verify this strategy. Our new method is substantially more sensitive than both the conventional intensity-only thresholding (IOT) method and the previous cluster method for signal change less than 6%, with maximum significant enhancement in sensitivity of 12.8 and 3.8 times, respectively. The results obtained from normal volunteers with visual stimulation further confirm the effectiveness of our new approach and show an average increase in detected activation area of 3.1 times over the IOT method and of 1.6 times over the previous cluster method using the new approach. ©1996 Wiley-Liss, Inc.
Article
A new computational method for the maximum likelihood solution in factor analysis is presented. This method takes into account the fact that the likelihood function may not have a maximum in a point of the parameter space where all unique variances are positive. Instead, the maximum may be attained on the boundary of the parameter space where one or more of the unique variances are zero. It is demonstrated that suchimproper (Heywood) solutions occur more often than is usually expected. A general procedure to deal with such improper solutions is proposed. The proposed methods are illustrated using two small sets of empirical data, and results obtained from the analyses of many other sets of data are reported. These analyses verify that the new computational method converges rapidly and that the maximum likelihood solution can be determined very accurately. A by-product obtained by the method is a large sample estimate of the variance-covariance matrix of the estimated unique variances. This can be used to set up approximate confidence intervals for communalities and unique variances.
Article
The auditory system serves a dual function of identifying sound objects and localizing sounds in space. Where in the cerebral cortex are these dual functions of hearing to be found? Neurons in primary auditory cortex (A1) respond primarily to tones of a single frequency. However, several additional areas have been identified recently both physiologically and anatomically in auditory association cortex surrounding A1. More complex response properties are encountered in these areas of the auditory belt suggesting functional specialization. In addition, the anatomical projections of the different belt areas target more remote regions in parietal and prefrontal cortex that are known to subserve specific functions. Parietal cortex, for instance, participates in spatial analysis; different areas of prefrontal cortex are involved in the processing of space and object information. In humans, functional neuroimaging has made specialized auditory processing streams especially evident by lighting up cortical areas that are jointly activated during specific tasks. This article summarizes recent evidence from both human and nonhuman primates supporting the existence of specialized processing streams in auditory association cortex.
Article
The brain uses context and prior knowledge to repair degraded sensory inputs and improve perception. For example, listeners hear speech continuing uninterrupted through brief noises, even if the speech signal is artificially removed from the noisy epochs. In a functional MRI study, we show that this temporal filling-in process is based on two dissociable neural mechanisms: the subjective experience of illusory continuity, and the sensory repair mechanisms that support it. Areas mediating illusory continuity include the left posterior angular gyrus (AG) and superior temporal sulcus (STS) and the right STS. Unconscious sensory repair occurs in Broca's area, bilateral anterior insula, and pre-supplementary motor area. The left AG/STS and all the repair regions show evidence for word-level template matching and communicate more when fewer acoustic cues are available. These results support a two-path process where the brain creates coherent perceptual objects by applying prior knowledge and filling-in corrupted sensory information.
Article
Verbal fluency is a classic neuropsychological measure of language production. Phonological verbal fluency involves the generation of words beginning with a specified letter, and its functional neuroanatomy is comprised of a distributed network of regions which is modulated by cognitive load. In order to investigate the functional relationship of these regions, the effective connectivity was analyzed with covariance structural equation modeling under conditions of varying cognitive load. Significant path coefficients were evident between the anterior cingulate, left middle frontal gyrus, and precuneus. The left middle frontal gyrus showed a facilitory projection to the precuneus which had a suppressive influence on anterior cingulate activation. With increasing cognitive demand, the left middle frontal projection to the precuneus became suppressive, and the path coefficient from the precuneus to the anterior cingulate showed a marked diminution in strength. The path analysis suggests that the lead-in process for letter verbal fluency may primarily involve an orthographic visual strategy. The marked changes in path coefficients with the increased cognitive load may reflect the greater demands placed on executive function. The significant changes in path coefficient values with increased cognitive demand indicate the importance of accounting for task difficulty not only in the interpretation of brain activation maps but also for effective connectivity measurements.