A study of the reproducibility and etiology of diffusion anisotropy differences in developmental stuttering: a potential role for impaired myelination.

Several diffusion tensor imaging (DTI) studies have reported fractional anisotropy (FA) reductions within the left perisylvian white matter (WM) of persistent developmental stutterers (PSs). However, these studies have not reached the same conclusions in regard to the presence, spatial distribution (focal/diffuse), and directionality (elevated/reduced) of FA differences outside of the left perisylvian region. In addition, supplemental DTI measures (axial and radial diffusivities, diffusion trace) have yet to be utilized to examine the potential etiology of these FA reductions. Therefore, the present study sought to reexamine earlier findings through a sex- and age-controlled replication analysis and then to extend these findings with the aforementioned non-FA measures. The replication analysis showed that robust FA reductions in PSs were largely focal, left hemispheric, and within late-myelinating associative and commissural fibers (division III of the left superior longitudinal fasciculus, callosal body, forceps minor of the corpus callosum). Additional DTI measures revealed that these FA reductions were attributable to an increase in diffusion perpendicular to the affected fiber tracts (elevated radial diffusivity). These findings suggest a hypothesis that will be testable in future studies: that myelogenesis may be abnormal in PSs within left-hemispheric fiber tracts that begin a prolonged course of myelination in the first postnatal year.

The Shb signalling scaffold binds to and regulates constitutive signals from the Epstein-Barr virus LMP2A membrane protein.

The Epstein-Barr virus latency-associated membrane protein LMP2A has been shown to activate the survival kinase Akt in epithelial and B cells in a phosphoinositide 3-kinase-dependent fashion. In this study, we demonstrate that the signalling scaffold Shb associates through SH2 and PTB domain interactions with phosphorylated tyrosine motifs in the LMP2A N-terminal tail. Additionally, we show that mutation of tyrosines in these motifs as well as shRNA-mediated downregulation of Shb leads to a loss of constitutive Akt-activation in LMP2A-expressing cells. Furthermore, utilization by Shb of the LMP2A ITAM motif regulates stability of the Syk tyrosine kinase in LMP2A-expressing cells. Our data set the precedent for viral utilization of the Shb signalling scaffold and implicate Shb as a regulator of LMP2A-dependent Akt activation.

On valid and reliable identification of normal disfluencies and stuttering disfluencies: a response to Aram, Meyers, and Ekelman (1990)

Aram, Meyers, and Ekelman (1990, Brain and Language, 38, 105-121) recently reported finding that children with unilateral brain lesions produced more stuttering-type nonfluencies than their neurologically normal peers. However, they did not report inter- or intrajudge agreement for the nonfluency types or for their method of measuring speech rate. The speech rates they reported were also unusually fast. We argue that these problems with Aram et al.'s study imperil both their results and their conclusions regarding developmental stuttering.

Is overt stuttered speech a prerequisite for the neural activations associated with chronic developmental stuttering?

Four adult right-handed chronic stutterers and four age-matched controls completed H(2)(15)O PET scans involving overt and imagined oral reading tasks. During overt stuttered speech prominent activations occurred in SMA (medial), BA 46 (right), anterior insula (bilateral), and cerebellum (bilateral) plus deactivations in right A2 (BA 21/22). These activations and deactivations also occurred when the same stutterers imagined they were stuttering. Some parietal regions were significantly activated during imagined stuttering, but not during overt stuttering. Most regional activations changed in the same direction when overt stuttering ceased (during chorus reading) and when subjects imagined that they were not stuttering (also during chorus reading). Controls displayed fewer similarities between regional activations and deactivations during actual and imagined oral reading. Thus overt stuttering appears not to be a prerequisite for the prominent regional activations and deactivations associated with stuttering.

Identifying the authoritative judgments of stuttering: comparisons of self-judgments and observer judgments.

Reliable and accurate stuttering measurement depends on the existence of unambiguous descriptions or exemplars of stuttered and nonstuttered speech. The development of clinically meaningful and useful exemplars, in turn, requires determining whether persons who stutter judge the same speech to be stuttered that other observers judge to be stuttered. The purpose of these experiments, therefore, was to compare stuttering judgements from several sources: 15 adults who stutter, judging their own spontaneous speech; the same adults who stutter, judging each other's speech; and a panel of 10 authorities on stuttering research and treatment. Judgments were mode under several conditions, including self-judgments made while the speaker was talking and self- and other-judgements made from recordings in continuous and interval formats. Results showed substantial differences in stuttering judgments across speakers, judges, and judgment conditions, but across-task comparisons were complicated by low self-agreement for many judges. Some intervals were judged consistently by all judges to be Stuttered or Nonstuttered, across multiple conditions, but many other intervals were either not assigned replicable judgments or were consistently judged to be Nonstuttered by the speaker who had produced them but were not assigned consistent judgments by other judges. The implications of these findings for stuttering measurement are considered.

Effects of time-interval judgement training on real-time measurement of stuttering.

The purpose of this study was to investigate whether a previously developed interval-based training program could improve judges' stuttering event judgments. Two groups of judges made real-time stuttering event judgments (computer-mouse button presses) in 3 to 6 trials before the response-contingent judgment training program and in another 3 to 6 trials after training, for recordings of 9 adults who stuttered. Their judgments were analyzed in terms of number of stuttering events, duration of stuttering, and 5-s intervals of speech that could be categorized as judged (or not judged) to contain stuttering. Results showed (a) changes in the amount of stuttering identified by the judges; (b) improved correspondence between the judges' identifications of stuttering events and interval-based standards previously developed from judgments made by experienced, authoritative judges; (c) improved correspondence between interval-based analyses of the judges' stuttering judgments and the previously developed standards; (d) improved intrajudge agreement; (e) improved interjudge agreement; and (f) convergence between the 2 judge groups, for samples and speakers used during training tasks and also for other speakers. Some implications of these findings for developing standardized procedures for the real-time measurement of stuttering are discussed.

Effect of speech dialect on speech naturalness ratings: a systematic replication of Martin, Haroldson, and Triden (1984).

This study investigated the effect of speech dialect on listeners' speech naturalness ratings by systematically replicating Martin, Haroldson, and Triden's (1984) study using three groups of speaker samples. Two groups consisted of speakers with General American dialect--one with persons who stutter and the other with persons who do not stutter. The third group also consisted of speakers who do not stutter but who spoke non-General American dialect. The results showed that speech naturalness ratings distinguished among the three speaker groups. The variables that appeared to influence speech naturalness ratings were type of dialect, speech fluency, and speaking rate, though they differed across speaker groups. The findings also suggested that strength of speech dialect may be a scaleable dimension that judges can rate with acceptable levels of reliability. Dialect may also be an important factor that needs to be incorporated or controlled within systems designed to train speech naturalness ratings. It may also be an important factor in determining the extent to which stuttering treatment produces natural sounding speech.

Children recovered from stuttering without formal treatment: perceptual assessment of speech normalcy.

Current evidence suggests that young children who recover from stuttering are essentially stutter-free. However, there is no evidence to indicate if their speech is perceptually indistinguishable from normally fluent peers or whether they retain perceptually unusual speech. One important example of recovery from stuttering is children who have recovered without receiving formal treatment. An investigation was conducted to determine if the speech of these children is perceptually different from the speech of children who have never stuttered. Speakers consisted of 10 preschool and early school-age children documented as recovered from stuttering without benefit of formal treatment. In a series of studies they were compared with 10 children who had never stuttered. Three groups of judges-sophisticated, unsophisticated, and experienced-were separately asked, using videotaped speech samples of the children, to decide which samples were from children who used to stutter. Results revealed that the children who recovered from stuttering were perceptually indistinguishable from the normal controls. The same result was obtained regardless of whether the samples were presented in paired-stimulus or single-stimulus mode. Two of the groups of judges were also instructed to rate the speech naturalness of the speech samples. The speakers were not distinguished on this measure either. Methodological issues and the implications of the findings are discussed.

The modification of speech naturalness during rhythmic stimulation treatment of stuttering.

This study investigated the modification of speech naturalness during stuttering treatment. It systematically replicated an earlier study (Ingham & Onslow, 1985) that demonstrated that unnatural-sounding stutter-free speech could be shaped into more natural-sounding stutter-free speech by using regular feedback of speech-naturalness ratings during speaking tasks. In the present study, the some procedure was used with three persons who stutter-2 adolescent girls and 1 adult man-during rhythmic stimulation conditions. The two adolescent participants spoke only English, but Spanish was the first and English the second language (ESL) of the adult participant. For the 2 adolescents, it was demonstrated that their unnatural-sounding rhythmic speech could be shaped to levels found among normally fluent speakers without losing the fluency-inducing benefits of rhythmic speech. The findings indicate that speech-naturalness feedback may be a powerful procedure for overcoming a problematic aspect of rhythmic speech treatments of stuttering. However, it was not possible to deliver reliable speech-naturalness feedback to the adult ESL speaker, who also displayed a strong dialect. The study highlights the need to find strategies to improve interjudge agreement when using speech naturalness ratings with speakers who display a strong dialect.

Experimental investigation of the effects of frequency-altered auditory feedback on the speech of adults who stutter.

A series of single-subject experiments evaluated the effects of frequency-altered auditory feedback (FAF) on the speech performance of four adult males who stutter. Using alterations of plus or minus one octave, FAF was compared with normal auditory feedback (NAF) in oral reading and spontaneous speech with measurements made of stuttered intervals, stutter-free speech rate, and speech naturalness. The effects of extended FAF conditions on spontaneous speech were also evaluated for two subjects who demonstrated a positive response to FAF. Results showed no consistencies across subjects in responses to FAF: One subject showed no response, another produced an initial temporary response, a third showed a deterioration in speech quality with minimal reductions in stuttering, and a fourth displayed substantial and sustained improvements in speech performance. Some implications of these findings for current research and theory about the relationship between stuttering and FAF are discussed.

Evaluation of a stuttering treatment based on reduction of short phonation intervals.

This paper reports the results of an efficacy study of a stuttering treatment program known as Modifying Phonation Intervals (MPI), which trains stuttering speakers to reduce the frequency of relatively short phonation intervals (PIs) during connected speech across speaking tasks and situations. Five young adult male stuttering speakers were treated in this computer-based program that systematically trains speakers to reduce selected short PIs found to functionally control stuttering. The treatment process was evaluated using multiple-baseline designs. Treatment was largely self-managed and based on a performance-contingent schedule of within-clinic speaking tasks (Establishment), beyond-clinic speaking tasks (Transfer), and systematic decreases in assessment occasions (Maintenance). Assessments were made at regular intervals before, during, and after treatment. All speakers achieved stutter-free and natural-sounding speech during within- and beyond-clinic speaking tasks at the completion of Maintenance. All were tested 12 months after completion of Maintenance, and all maintained the results. The findings from this study suggest that this procedure may make a significant contribution to stuttering treatment practice.

Brain imaging studies of developmental stuttering.

UNLABELLED: This paper reviews recent brain imaging research on stuttering against a background of studies that the writer and colleagues have been conducting at the University of Texas Health Science Center in San Antonio. The paper begins by reviewing some pertinent background to recent neuroimaging investigations of developmental stuttering. It then outlines the findings from four brain imaging studies that the San Antonio group has conducted using H2(15)O positron emission tomography (PET). Finally, some of the principal findings that are emerging across brain imaging studies of stuttering are reviewed, while also highlighting--and attempting to resolve--some apparent across-study inconsistencies among the findings. Research on stuttering using magnetoencephalogaphy (MEG) and transcranial magnetic stimulation (TMS) is also considered. The findings increasingly point to a failure of normal temporal lobe activation during speech that may either contribute to (or is the result of) a breakdown in the sequencing of processing among premotor regions implicated in phonologic planning. LEARNING OUTCOMES: As a result of this activity, the participant will become familiar with some recent neurophysiological correlates of stuttering and what they suggest about the nature of this disorder.

On token reinforcement and stuttering therapy: another view on findings reported by Howie and Woods (1982).

Howie and Woods (1982) have provided data that, they claim, indicate that a token reinforcement system is redundant in instating and shaping fluent speech within a stuttering treatment program developed by Ingham and Andrews (1973a, b). However, there were substantial procedural differences between the treatment programs referred to in both studies, as well as methodological weaknesses in Howie and Woods' study. These factors provide ample sources of explanation for Howie and Woods' failure to demonstrate benefits from their token reinforcement system.

An analysis of a token economy in stuttering therapy.

A stuttering therapy program in which adult stutterers were hospitalized and treated in small groups (n = 4) under token economy conditions is described. The Token System reinforced reductions and penalized increases in stuttering during conversation. The therapy program was divided into three stages. Initially, subjects were treated by the token system, which was then integrated with a delayed auditory feedback schedule designed to instate and shape a prolonged speech pattern into normal fluent speech. Finally, subjects passed through a speech situation hierarchy while under token control conditions. Experiments conducted in the first two stages of treatment are described. The first-stage experiments examined the design of the token system; the second-stage experiment assessed the effect of a contingent punishment schedule integrated with the delayed auditory feedback procedure in order to shape rate of speaking as well as fluency.

On-line measurement of aphasic speech.

Seven response categories, devised for the concurrent evaluation of aphasic speech, were investigated for their reliability. The spontaneous speech of 5 aphasic subjects was rated on-line by 4 clinicians using 7 response categories. Agreement among the 4 judges, for both inter-judge and intra-judge reliability, varied for each subject and was not high enough to support the concurrent use of the seven response categories for the on-line investigation of aphasic speech in all subjects. Ways in which the reliability of the categories might be increased are discussed.

Aberrant expression and biological significance of Sox2, an embryonic stem cell transcriptional factor, in ALK-positive anaplastic large cell lymphoma.

Sox2 (sex-determining region Y-Box) is one of the master transcriptional factors that are important in maintaining the pluripotency of embryonic stem cells (ESCs). In line with this function, Sox2 expression is largely restricted to ESCs and somatic stem cells. We report that Sox2 is expressed in cell lines and tumor samples derived from ALK-positive anaplastic large cell lymphoma (ALK(+)ALCL), for which the normal cellular counterpart is believed to be mature T-cells. The expression of Sox2 in ALK(+)ALCL can be attributed to nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), the oncogenic fusion protein carrying a central pathogenetic role in these tumors. By confocal microscopy, Sox2 protein was detectable in virtually all cells in ALK(+)ALCL cell lines. However, the transcriptional activity of Sox2, as assessed using a Sox2-responsive reporter construct, was detectable only in a small proportion of cells. Importantly, downregulation of Sox2 using short interfering RNA in isolated Sox2(active) cells, but not Sox2(inactive) cells, resulted in a significant decrease in cell growth, invasiveness and tumorigenicity. To conclude, ALK(+)ALCL represents the first example of a hematologic malignancy that aberrantly expresses Sox2, which represents a novel mechanism by which NPM-ALK mediates tumorigenesis. We also found that the transcriptional activity and oncogenic effects of Sox2 can be heterogeneous in cancer cells.