Caviness, John N.

ABSTRACTBackgroundThe objective of this study was to evaluate citalopram for executive functioning in Huntington's disease (HD).MethodsThe study was randomized, double‐blind, and placebo‐controlled. Thirty‐three adults with HD, cognitive complaints, and no depression (Hamilton Depression [HAM‐D] rating scale ≤12) were administered citalopram 20 mg or placebo (7 visits, 20 weeks), with practice and placebo run‐ins. The primary outcome was change in executive functioning.ResultsThe intent to treat analysis was controlled for practice effects, comparing visits 1 and 2 to visits 5 and 6 for citalopram versus placebo. There were no significant benefits on the executive function composite (treatment‐placebo mean difference −0.167; 95% confidence interval [CI], −0.361 to 0.028; P = .092). Citalopram participants showed improved clinician‐rated depression symptoms on the HAM‐D (t = −2.02; P = 0.05). There were no group differences on motor ratings, self‐reported executive functions, psychiatric symptoms, or functional status.ConclusionsThere was no evidence that short‐term treatment with citalopram improved executive functions in HD. Despite excluding patients with active depression, participants on citalopram showed improved mood, raising the possibility of efficacy for subsyndromal depression in HD. © 2013 International Parkinson and Movement Disorder Society

Although intelligibility deficits are common across various forms of dysarthria, it was hypothesized that the causes of intelligibility reductions depend on the ways the degraded signal challenges listener cognitive-perceptual strategies. This hypothesis was confirmed by analyzing the lexical boundary errors (LBE) elicited by 44 speakers with one of four forms of dysarthria (ataxic, hypokinetic, hyperkinetic, mixed spastic-flaccid). Error patterns from 60 listener transcripts revealed reliance on metrical stress to segment the 80 six-syllable phrases. However, reductions and disturbances in the acoustic cues to syllabic stress associated with each form of dysarthria resulted in different LBE patterns. Explanations for these unique patterns are found, in part, in the metrical structures of the dysarthric speech. For example, the temporal relationships among stressed and unstressed syllables varied widely in hyperkinetic speech, which ostensibly prevented listeners from optimally exploiting metrical stress as a cue for segmentation. The equal-even temporal structure of the spastic-flaccid speech resulted in the highest proportion of boundary insertions. The presence of interword pauses facilitated the assignment of word onset to strong syllables. Results will be presented relative to models of lexical segmentation and clinical implications for targets of remediation in the dysarthrias. [Work supported from NIH-NIDCD 5R01 DC6859.]

The detrimental effect of speaker variability on word recognition has been reported using a wide variety of tasks and stimuli. In this study, the use of dysarthric speech alongside unimpaired speech allowed us to examine the effect of indexical variability from a new perspective. We compared voice-specificity effects in words produced by healthy speakers and the same words produced by dysarthric patients suffering from Huntington’s disease (HD). The speech of persons with HD is particularly suited to this issue because of its idiosyncratic and variable manifestation. Reaction time and accuracy results provided confirmatory evidence for Luce et al.’s (2003) time-course hypothesis: The slower responses occasioned by processing dysarthric stimuli were accompanied with greater reliance on surface details of the stimuli. Thus, specificity effects can be seen as resulting from a coping strategy called upon when the system is presented with an input that is highly dissimilar from canonical lexical representations. In addition, we found some evidence that the time-course hypothesis holds even when intelligibility is controlled. This finding confirms that time, rather than processing effort, is the cause of specificity effects, with activation confined to abstract representations in an early stage and spreading to episodic traces later on.

Disturbances in speech rhythm are common in dysarthria, and deficit patterns vary among dysarthria subtypes. Attempts to quantify differences in disordered rhythm patterns have met with limited success. Here, we attempt to differentiate various forms of dysarthria using metrics designed to quantify linguistic rhythm on a stress-timed versus syllable-timed continuum. Speakers with hypokinetic, ataxic, hyperkinetic, or mixed flaccid-spastic dysarthria read sentences. Rhythm metrics were calculated for these utterances based on vocalic and consonantal interval durations. Differences among groups were discovered for %V (percentage of utterance duration comprised of vocalic intervals), VarcoV (rate-normalized standard deviation of vocalic interval durations), and nPVI-V (normalized pairwise variability index for vocalic intervals). Differences were independent of variable speaking rates among groups. All dysarthric groups produced rhythm patterns less stress-timed than the control American English speakers, with lower VarcoV and nPVI-V and higher %V. Those with flaccid-spastic dysarthria secondary to amyotrophic lateral sclerosis exhibited a syllable-timed pattern more extreme than even control Spanish speakers, indicating minimal differentiation of stressed and unstressed syllables. These results show that the various types of rhythmic disturbance accompanying dysarthria can be effectively described and distinguished within a stress-/syllable-timed continuum and relative to healthy speech.

Abstract Background: The etiology and natural history of Parkinson’s disease (PD) are not well understood. Some non-motor symptoms such as hyposmia, rapid eye movement sleep behavior disorder, and constipation may develop during the prodromal stage of PD and precede PD diagnosis by years. Objectives: We examined the promise and pitfalls of research on premotor symptoms of PD and developed priorities and strategies to understand their clinical and etiological implications. Methods: This review was based on a workshop, Parkinson’s Disease Premotor Symptom Symposium, held 7–8 June 2012 at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina. Discussion: Research on premotor symptoms of PD may offer an excellent opportunity to characterize high-risk populations and to better understand PD etiology. Such research may lead to evaluation of novel etiological hypotheses such as the possibility that environmental toxicants or viruses may initiate PD pathogenesis in the gastrointestinal tract or olfactory bulb. At present, our understanding of premotor symptoms of PD is in its infancy and faces many obstacles. These symptoms are often not specific to PD and have low positive predictive value for early PD diagnosis. Further, the pathological bases and biological mechanisms of these premotor symptoms and their relevance to PD pathogenesis are poorly understood. Conclusion: This is an emerging research area with important data gaps to be filled. Future research is needed to understand the prevalence of multiple premotor symptoms and their etiological relevance to PD. Animal experiments and mechanistic studies will further understanding of the biology of these premotor symptoms and test novel etiological hypothesis. Citation: Chen H, Burton EA, Ross GW, Huang X, Savica R, Abbott RD, Ascherio A, Caviness JN, Gao X, Gray KA, Hong JS, Kamel F, Jennings D, Kirshner A, Lawler C, Liu R, Miller GW, Nussbaum R, Peddada SD, Comstock Rick A, Ritz B, Siderowf AD, Tanner CM, Tröster AI, Zhang J. 2013. Research on the premotor symptoms of Parkinson’s Disease: clinical and etiological implications. Environ Health Perspect 121:1245–1252; http://dx.doi.org/10.1289/ehp.1306967