Decreased Cerebellar-Orbitofrontal Connectivity Correlates with Stuttering Severity: Whole-Brain Functional and Structural Connectivity Associations with Persistent Developmental Stuttering.
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ABSTRACT:
SUBMITTER: Sitek KR
PROVIDER: S-EPMC4855981 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Persistent developmental stuttering (PDS) is a speech disorder that impairs communication skills. Despite extensive research, the core causes of PDS are elusive. Converging evidence from task-induced neuroimaging methods has demonstrated the contributions of the basal ganglia and the cerebellum to PDS, but such task-state neuroimaging findings are often confounded by behavioral performance differences between subjects who stutter and normal controls. Here, using resting-state functional magnetic resonance imaging, we investigated functional connectivity within cerebellar-cortical and basal ganglia-thalamocortical networks in 16 adults who stutter and 18 age-matched fluent speakers. Seed-to-voxel analysis demonstrated that, compared to controls, adults who stutter showed alternations in functional connectivity of cerebellum to motor cortex as well as connectivity among different locals within cerebellum. Additionally, we found that functional connectivity within cerebellar circuits was significantly correlated with severity of stuttering. The alternations of functional connectivity within basal ganglia-thalamocortical networks were identified as the reduced connectivity of the putamen to the superior temporal gyrus and inferior parietal lobules in adults who stutter. The abnormalities of resting state functional connectivity are assumed to affect language planning and motor execution critical for speaking fluently. Our findings may yield neurobiological cues to the biomarkers of PDS.
| S-EPMC4705486 | biostudies-other
Project description:IntroductionIndividuals 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.MethodsParticipants 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.ResultsThe 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.ConclusionsOur 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.
| S-EPMC8821245 | biostudies-literature
Project description:Persistent stuttering is a prevalent neurodevelopmental speech disorder, which presents with involuntary speech blocks, sound and syllable repetitions, and sound prolongations. Affected individuals often struggle with negative feelings, elevated anxiety, and low self-esteem. Neuroimaging studies frequently link persistent stuttering with cortical alterations and dysfunctional cortico-basal ganglia-thalamocortical loops; dMRI data also point toward connectivity changes of the superior longitudinal fasciculus (SLF) and the frontal aslant tract (FAT). Both tracts are involved in speech and language functions, and the FAT also supports inhibitory control and conflict monitoring. Whether the two tracts are involved in therapy-associated improvements and how they relate to therapeutic outcomes is currently unknown. Here, we analyzed dMRI data of 22 patients who participated in a fluency-shaping program, 18 patients not participating in therapy, and 27 fluent control participants, measured 1 year apart. We used diffusion tractography to segment the SLF and FAT bilaterally and to quantify their microstructural properties before and after a fluency-shaping program. Participants learned to speak with soft articulation, pitch, and voicing during a 2-week on-site boot camp and computer-assisted biofeedback-based daily training for 1 year. Therapy had no impact on the microstructural properties of the two tracts. Yet, after therapy, stuttering severity correlated positively with left SLF fractional anisotropy, whereas relief from the social-emotional burden to stutter correlated negatively with right FAT fractional anisotropy. Thus, posttreatment, speech motor performance relates to the left dorsal stream, while the experience of the adverse impact of stuttering relates to the structure recently associated with conflict monitoring and action inhibition.
| S-EPMC9248304 | biostudies-literature
Project description:Motor balance in developmental stuttering (DS) was investigated with Transcranial Magnetic Stimulation (TMS), with the aim to define novel neural markers of persistent DS in adulthood. Eleven DS adult males were evaluated with TMS on tongue primary motor cortex, compared to 15 matched fluent speakers, in a "state" condition (i.e. stutterers vs. fluent speakers, no overt stuttering). Motor and silent period thresholds (SPT), recruitment curves, and silent period durations were acquired by recording tongue motor evoked potentials. Tongue silent period duration was increased in DS, especially in the left hemisphere (P<0.05; Hedge's g or Cohen's dunbiased = 1.054, i.e. large effect size), suggesting a "state" condition of higher intracortical inhibition in left motor cortex networks. Differences in motor thresholds (different excitatory/inhibitory ratios in DS) were evident, as well as significant differences in SPT. In fluent speakers, the left hemisphere may be marginally more excitable than the right one in motor thresholds at lower muscular activation, while active motor thresholds and SPT were higher in the left hemisphere of DS with respect to the right one, resulting also in a positive correlation with stuttering severity. Pre-TMS electromyography data gave overlapping evidence. Findings suggest the existence of a complex intracortical balance in DS tongue primary motor cortex, with a particular interplay between excitatory and inhibitory mechanisms, also in neural substrates related to silent periods. Findings are discussed with respect to functional and structural impairments in stuttering, and are also proposed as novel neural markers of a stuttering "state" in persistent DS, helping to define more focused treatments (e.g. neuro-modulation).
| S-EPMC5053488 | biostudies-literature
Project description:Vibrational energy created at the larynx during speech will deflect vestibular mechanoreceptors in humans (Todd et al., 2008; Curthoys, 2017; Curthoys et al., 2019). Vestibular-evoked myogenic potential (VEMP), an indirect measure of vestibular function, was assessed in 15 participants who stutter, with a non-stutter control group of 15 participants paired on age and sex. VEMP amplitude was 8.5 dB smaller in the stutter group than the non-stutter group (p = 0.035, 95% CI [-0.9, -16.1], t = -2.1, d = -0.8, conditional R 2 = 0.88). The finding is subclinical as regards gravitoinertial function, and is interpreted with regard to speech-motor function in stuttering. There is overlap between brain areas receiving vestibular innervation, and brain areas identified as important in studies of persistent developmental stuttering. These include the auditory brainstem, cerebellar vermis, and the temporo-parietal junction. The finding supports the disruptive rhythm hypothesis (Howell et al., 1983; Howell, 2004) in which sensory inputs additional to own speech audition are fluency-enhancing when they coordinate with ongoing speech.
| S-EPMC8477904 | biostudies-literature
Project description:Stuttering is a common but poorly understood speech disorder. Consistent evidence for the involvement of genetic factors in stuttering has motivated studies aimed at identifying causative genetic variants that could shed light on the underlying molecular and cellular deficits in this disorder. Such studies have begun to identify causative genes. The purpose of this review is to summarize the gene discoveries to date, and to cover the subsequent functional studies that are beginning to provide insights into how these gene mutations might cause stuttering. Surprisingly, the first variant genes to be associated with stuttering are those encoding the lysosomal targeting system, GNPTAB, GNPTG, and NAGPA. Although mutations in NAGPA have not been associated with a disorder in humans, mutations in GNPTAB and GNPTG cause mucolipidosis types II and III, which are rare autosomal recessive lysosomal storage disorders, associated with pathology of bone, connective tissue, liver, spleen, and brain. Analysis of mutations in these genes has so far identified predominantly missense mutations in stuttering, in contrast to the truncating and other mutations that result in very low GNPTAB/G enzyme activity and are historically associated with mucolipidosis. Genetic evidence for the role of lysosomal targeting mutations in stuttering has now been buttressed by biochemical studies of the mutant enzymes found in this disorder. While data on the GlcNAc-phosphotransferase encoded by GNPTAB/G remains limited and only suggestive, a study of the enzyme encoded by NAGPA has shown that the mutations found in stuttering reduce the overall cellular activity of this enzyme by about half, and that they result in deficits in intracellular processing and trafficking that lead to a reduced cellular half life. How these deficits result in the presumed speech-specific neuropathology associated with stuttering is not yet known. However these findings have opened several new lines of inquiry, including studies in mice carrying human stuttering mutations, that represent promising approaches to this disorder.
| S-EPMC3483359 | biostudies-literature
Project description:A neuronal sign of persistent developmental stuttering is the magnified coactivation of right frontal brain regions during speech production. Whether and how stuttering severity relates to the connection strength of these hyperactive right frontal areas to other brain areas is an open question. Scrutinizing such brain-behaviour and structure-function relationships aims at disentangling suspected underlying neuronal mechanisms of stuttering. Here, we acquired diffusion-weighted and functional images from 31 adults who stutter and 34 matched control participants. Using a newly developed structural connectivity measure, we calculated voxel-wise correlations between connection strength and stuttering severity within tract volumes that originated from functionally hyperactive right frontal regions. Correlation analyses revealed that with increasing speech motor deficits the connection strength increased in the right frontal aslant tract, the right anterior thalamic radiation, and in U-shaped projections underneath the right precentral sulcus. In contrast, with decreasing speech motor deficits connection strength increased in the right uncinate fasciculus. Additional group comparisons of whole-brain white matter skeletons replicated the previously reported reduction of fractional anisotropy in the left and right superior longitudinal fasciculus as well as at the junction of right frontal aslant tract and right superior longitudinal fasciculus in adults who stutter compared to control participants. Overall, our investigation suggests that right fronto-temporal networks play a compensatory role as a fluency enhancing mechanism. In contrast, the increased connection strength within subcortical-cortical pathways may be implied in an overly active global response suppression mechanism in stuttering. Altogether, this combined functional MRI-diffusion tensor imaging study disentangles different networks involved in the neuronal underpinnings of the speech motor deficit in persistent developmental stuttering.
| S-EPMC5837552 | biostudies-literature
Project description: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.
| S-EPMC6865627 | biostudies-literature
Project description:ObjectiveTo explore the interhemispheric functional coordination following traumatic brain injury (TBI) and its association with posttraumatic anxiety and depressive symptoms.MethodsThis was a combination of a retrospective cohort study and a cross-sectional observational study. We investigated the functional coordination between hemispheres by voxel-mirrored homotopic connectivity (VMHC). Grey matter volumes were examined by voxel-based morphometry (VBM), and microstructural integrity of the corpus callosum (CC) was assessed by diffusion tension imaging (DTI). The anxiety and depressive symptoms were evaluated with the Hospital Anxiety and Depression Scale.ResultsThe VMHC values of the bilateral middle temporal gyrus (MTG) and orbital middle frontal gyrus (MFG) were significantly decreased in TBI patients versus the healthy controls. Weakened homotopic functional connectivity (FC) in the bilateral orbital MFG is moderate positively correlated with anxiety and depressive symptoms. The white matter integrity in the CC was extensively reduced in TBI patients. In the receiver operating characteristic analysis, the VMHC value of the orbital MFG could distinguish TBI from HC with an area under the curve of 0.939 (sensitivity of 1 and specificity of 0.867).ConclusionTBI disrupts the interhemispheric functional and structural connection, which is correlated with posttraumatic mood disorders. These findings may serve as a clinical indicator for diagnosis.
| S-EPMC9012975 | biostudies-literature
Project description:The cerebellum's role in nonmotor processes is now well accepted, but cerebellar interaction with cerebral targets is not well understood. Complex cognitive tasks activate cerebellar, parietal, and frontal regions, but the effective connectivity between these regions has never been tested. To this end, we used psycho-physiological interactions (PPI) analysis to test connectivity changes of cerebellar and parietal seed regions in complex (2-digit by 1-digit multiplication, e.g., 12 × 3) vs. simple (1-digit by 1-digit multiplication, e.g., 4 × 3) task conditions ("complex - simple"). For cerebellar seed regions (lobule VI, hemisphere and vermis), we found significantly decreased cerebellar-parietal, cerebellar-cingulate, and cerebellar-frontal connectivity in complex multiplication. For parietal seed regions (PFcm, PFop, PFm) we found significantly increased parietal-parietal and parietal-frontal connectivity in complex multiplication. These results suggest that decreased cerebellar-cerebral connectivity contributes to complex task performance. Interestingly, BOLD activity contrasts revealed partially overlapping parietal areas of increased BOLD activity but decreased cerebellar-parietal PPI connectivity.
| S-EPMC5040373 | biostudies-literature