No abstract

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.

Charcot-Marie-Tooth disease type 2C (CMT2C) is an autosomal dominant neuropathy characterized by limb, diaphragm, and laryngeal muscle weakness. Two unrelated families with CMT2C showed significant linkage to chromosome 12q24.11. All genes in this region were sequenced and heterozygous missense mutations were identified in the TRPV4 gene at positions c.805C>T and c.806G>A, causing the amino acid substitutions R269C and R269H. TRPV4 is a well known member of the TRP superfamily of cation channels. In TRPV4-transfected cells, the CMT2C mutations caused marked cellular toxicity and increased constitutive and activated channel currents. Mutations in TRPV4 were previously associated with skeletal dysplasias. Our findings indicate that TRPV4 mutations can also cause a degenerative disorder of peripheral nerves. The CMT2C mutations lie in a distinct region of the TRPV4 ankyrin repeats, suggesting that this striking phenotypic variability may be due to differential effects on regulatory protein-protein interactions.

Stuttering is a developmental speech disorder that occurs in 5% of children with spontaneous remission in approximately 70% of cases. Previous imaging studies in adults with persistent stuttering found left white matter deficiencies and reversed right-left asymmetries compared to fluent controls. We hypothesized that similar differences might be present indicating brain development differences in children at risk of stuttering. Optimized voxel-based morphometry compared gray matter volume (GMV) and diffusion tensor imaging measured fractional anisotropy (FA) in white matter tracts in 3 groups: children with persistent stuttering, children recovered from stuttering, and fluent peers. Both the persistent stuttering and recovered groups had reduced GMV from normal in speech-relevant regions: the left inferior frontal gyrus and bilateral temporal regions. Reduced FA was found in the left white matter tracts underlying the motor regions for face and larynx in the persistent stuttering group. Contrary to previous findings in adults who stutter, no increases were found in the right hemisphere speech regions in stuttering or recovered children and no differences in right-left asymmetries. Instead, a risk for childhood stuttering was associated with deficiencies in left gray matter volume while reduced white matter integrity in the left hemisphere speech system was associated with persistent stuttering. Anatomical increases in right hemisphere structures previously found in adults who stutter may have resulted from a lifetime of stuttering. These findings point to the importance of considering the role of neuroplasticity during development when studying persistent forms of developmental disorders in adults.

The behavioral, cognitive, and electrophysiological effect of a single dose of dextroamphetamine (0.5 milligram per kilogram of body weight) or placebo was examined in 14 normal prepubertal boys (mean age, 10 years 11 months) in a double-blind study. When amphetamine was given, the group showed a marked decrease in motor activity and reaction time and improved performance on cognitive tests. The similarity of the response observed in normal children to that reported in children with "hyperactivity" or minimal brain dysfunction casts doubt on pathophysiological models of minimal brain dysfunction which assume that children with this syndrome have a clinically specific or "paradoxical" response to stimulants.