Janis C. Ingham

Imaging human intra-cerebral connectivity by PET during TMS

NON-INVASIVE imaging of human inter-regional neural connectivity by positron emission tomography (PET) during transcranial magnetic stimulation (TMS) was performed. The hand area of primary motor cortex (M1) in the left cerebral hemisphere was stimulated with TMS while local and remote effects were recorded with PET. At the stimulated site, TMS increased blood flow (12–20%) in a highly focal manner, without an inhibitory surround. Remote covariances, an index of connectivity with M1, were also focal. Connectivity patterns established in non-human species were generally confirmed. Excitatory connectivity (positive covariance) was observed in ipsilateral primary and secondary somatosensory areas (S1 and S2), in ipsilateral ventral, lateral premotor cortex (M2) and in contralateral supplementary motor area (SMA). Inhibitory connectivity (negative covariance) was observed in contralateral M1.

Hypophonia in Parkinson’s disease: Neural correlates of voice treatment revealed by PET

Objective: To investigate the neural correlates of hypophonia in individuals with idiopathic PD (IPD) before and after voice treatment with the Lee Silverman Voice Treatment method (VT) using 15O-H2O PET. Methods: Regional cerebral blood flow (rCBF) changes associated with overt speech–motor tasks relative to the resting state were measured in the IPD subjects before and after VT, and in a group of healthy control volunteers. Results: Behavioral measures of voice loudness significantly improved following treatment. Before VT, patients had strong speech-related activations in motor and premotor cortex (M1-mouth, supplementary motor cortex [SMA], and inferior lateral premotor cortex [ILPm]), which were significantly reduced post-VT. Similar to the post-treatment session, premotor activations were absent (SMA) or below statistical threshold (M1-mouth) in the healthy control group. In addition, following VT treatment, significant right-sided activations were present in anterior insular cortex, caudate head, putamen, and dorsolateral prefrontal cortex (DLPFC). Finally, the VT-induced neural changes were not present with transient experimenter-cued increases of loudness in VT-untreated patients. Conclusions: Effective improvement of IPD hypophonia following voice treatment with VT was accompanied by a reduction of cortical motor–premotor activations, resembling the functional pattern observed in healthy volunteers and suggesting normalization, and additional recruitment of right anterior insula, caudate head, putamen, and DLPFC. This treatment-dependent functional reorganization suggests a shift from an abnormally effortful (premotor cortex) to a more automatic (basal ganglia, anterior insula) implementation of speech–motor actions.

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.

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.

Brain activity in adults who stutter: Similarities across speaking tasks and correlations with stuttering frequency and speaking rate

Many differences in brain activity have been reported between persons who stutter (PWS) and typically fluent controls during oral reading tasks. An earlier meta-analysis of imaging studies identified stutter-related regions, but recent studies report less agreement with those regions. A PET study on adult dextral PWS (n=18) and matched fluent controls (CONT, n=12) is reported that used both oral reading and monologue tasks. After correcting for speech rate differences between the groups the task-activation differences were surprisingly small. For both analyses only some regions previously considered stutter-related were more activated in the PWS group than in the CONT group, and these were also activated during eyes-closed rest (ECR). In the PWS group, stuttering frequency was correlated with cortico-striatal-thalamic circuit activity in both speaking tasks. The neuroimaging findings for the PWS group, relative to the CONT group, appear consistent with neuroanatomic abnormalities being increasingly reported among PWS.

Evidence-based treatment of stuttering: I. Definition and application

UNLABELLED The philosophy guiding evidence-based treatment and its application to decision-making in stuttering treatment is described. Limitations to the use of evidence-based treatment principles to guide stuttering treatment, namely the lack of a substantial treatment research literature that can serve as the basis for meta-analyses and systematic reviews of effective treatment studies, are bemoaned. Guidelines are provided to aid clinicians in their own conduct of critical evaluations of treatment research. EDUCATIONAL OBJECTIVES The reader will learn about and be able to (1) describe the four steps that characterize evidence-based practice, (2) evaluate previous efforts to develop practice guidelines for stuttering, (3) assess the importance of an evidence-based approach to stuttering treatment, and (4) discuss the need for more research that will contribute to the evidence base.

Individual differences in neural regions functionally related to real and imagined stuttering.

Recent brain imaging investigations of developmental stuttering show considerable disagreement regarding which regions are related to stuttering. These divergent findings have been mainly derived from group studies. To investigate functional neurophysiology with improved precision, an individual-participant approach (N=4) using event-related functional magnetic resonance imaging and test-retest reliability measures was performed while participants produced fluent and stuttered single words during two separate occasions. A parallel investigation required participants to imagine stuttering or not stuttering on single words. The overt and covert production tasks produced considerable within-subject agreement of activated voxels across occasions, but little within-subject agreement between overt and covert task activations. However, across-subject agreement for regions activated by the overt and covert tasks was minimal. These results suggest that reliable effects of stuttering are participant-specific, an implication that might correspond to individual differences in stuttering severity and functional compensation due to related structural abnormalities.

Anomalous White Matter Morphology in Adults Who Stutter

AIMS Developmental stuttering is now generally considered to arise from genetic determinants interacting with neurologic function. Changes within speech-motor white matter (WM) connections may also be implicated. These connections can now be studied in great detail by high-angular-resolution diffusion magnetic resonance imaging. Therefore, diffusion spectrum imaging was used to reconstruct streamlines to examine white matter connections in people who stutter (PWS) and in people who do not stutter (PWNS). METHOD WM morphology of the entire brain was assayed in 8 right-handed male PWS and 8 similarly aged right-handed male PWNS. WM was exhaustively searched using a deterministic algorithm that identifies missing or largely misshapen tracts. To be abnormal, a tract (defined as all streamlines connecting a pair of gray matter regions) was required to be at least one 3rd missing, in 7 out of 8 subjects in one group and not in the other group. RESULTS Large portions of bilateral arcuate fasciculi, a heavily researched speech pathway, were abnormal in PWS. Conversely, all PWS had a prominent connection in the left temporo-striatal tract connecting frontal and temporal cortex that was not observed in PWNS. CONCLUSION These previously unseen structural differences of WM morphology in classical speech-language circuits may underlie developmental stuttering.

Regional brain activity change predicts responsiveness to treatment for stuttering in adults

Developmental stuttering is known to be associated with aberrant brain activity, but there is no evidence that this knowledge has benefited stuttering treatment. This study investigated whether brain activity could predict progress during stuttering treatment for 21 dextral adults who stutter (AWS). They received one of two treatment programs that included periodic H2(15)O PET scanning (during oral reading, monologue, and eyes-closed rest conditions). All participants successfully completed an initial treatment phase and then entered a phase designed to transfer treatment gains; 9/21 failed to complete this latter phase. The 12 pass and 9 fail participants were similar on speech and neural system variables before treatment, and similar in speech performance after the initial phase of their treatment. At the end of the initial treatment phase, however, decreased activation within a single region, L. putamen, in all 3 scanning conditions was highly predictive of successful treatment progress.

Stuttering treatment and brain research in adults: A still unfolding relationship

PURPOSE Brain imaging and brain stimulation procedures have now been used for more than two decades to investigate the neural systems that contribute to the occurrence of stuttering in adults, and to identify processes that might enhance recovery from stuttering. The purpose of this paper is to review the extent to which these dual lines of research with adults who stutter have intersected and whether they are contributing towards the alleviation of this impairment. METHOD Several areas of research are reviewed in order to determine whether research on the neurology of stuttering is showing any potential for advancing the treatment of this communication disorder: (a) attempts to discover the neurology of stuttering, (b) neural changes associated with treated recovery, and (c) direct neural intervention. RESULTS AND CONCLUSIONS Although much has been learned about the neural underpinnings of stuttering, little research in any of the reviewed areas has thus far contributed to the advancement of stuttering treatment. Much of the research on the neurology of stuttering that does have therapy potential has been largely driven by a speech-motor model that is designed to account for the efficacy of fluency-inducing strategies and strategies that have been shown to yield therapy benefits. Investigations on methods that will induce neuroplasticity are overdue. Strategies profitable with other disorders have only occasionally been employed. However, there are signs that investigations on the neurology of adults who have recovered from stuttering are slowly being recognized for their potential in this regard.