Self-paced timing detects and tracks change in prodromal Huntington disease.

Abstract

Objective This study compares self-paced timing performance (cross-sectionally and longitudinally) between participants with prodromal Huntington disease (pr-HD) and a comparison group of gene non-expanded participants from affected families (NC). Methods At baseline, participants in two groups (747 pr-HD: 188 NC) listened to tones presented at 550ms intervals, matched that pace by tapping response keys and continued the rhythm (self-paced) after the tone had stopped. Standardized cross-sectional and longitudinal linear models examined the relationships between self-paced timing precision and estimated proximity to diagnosis, and various other demographic factors. Results Pr-HD participants showed significantly less timing precision than NC. Cross-sectional comparison of pr-HD and NC participants showed a significant performance difference on two administration conditions of the task (dominant hand: p<.0001; alternating thumbs: p<.0001). Additionally, estimated proximity to diagnosis was related to timing precision in both conditions, (dominant hand: t=−11.14,df=920, p<.0001; alternating thumbs: t=−11.32, df=918, p<.0001), even considering demographic and experience variables. Longitudinal modeling showed that pr-HD participants worsen more quickly at the task than the NC group, and that decline rate increases with estimated proximity to diagnosis in both conditions (dominant hand: t=−2.85,df=417, p=.0045; alternating thumbs: t=−3.56, df= 445, p=.0004). Effect sizes based on adjusted mean annual change ranged from −0.34 to 0.25 in the longitudinal model. Conclusions The self-paced timing paradigm has potential for use as a screening tool and outcome measure in pr-HD clinical trials to gauge therapeutically-mediated improvement or maintenance of function.

Behavioral and In Vivo Electrophysiological Evidence for Presymptomatic Alteration of Prefrontostriatal Processing in the Transgenic Rat Model for Huntington Disease

“…Among these, a deficit in temporal discrimination has been reported to correlate with estimated age of onset (Paulsen et al, 2004;Beste et al, 2007). When timing was imbedded in motor processes, the deficit was clearly present in pre-HD subjects, even when tested well before the estimated disease onset (Hinton et al, 2007;Paulsen et al, 2008;Rowe et al, 2010). For these subsecond motor timing tasks, increased variability but good timing accuracy was reported.…”

Abnormal synchrony of resting state networks in premanifest and symptomatic Huntington disease: the IMAGE-HD study

“…We selected motor (i.e., precision of self-paced tapping fast [target rate of 3 Hz]) and cognitive (Stroop word reading and SDMT) tasks previously shown to be sensitive to progression of Huntington disease. 44,45 The calculation for timing precision is 1 ÷ the standard deviation of the intertap interval in seconds. 44,46 We also selected DBS as a symptom-free measure of gene expression across both Huntington disease groups.…”

“…44,45 The calculation for timing precision is 1 ÷ the standard deviation of the intertap interval in seconds. 44,46 We also selected DBS as a symptom-free measure of gene expression across both Huntington disease groups. We used SPSS version 16.0 to perform Spearman rank correlation.…”

Early Dysfunction of Neural Transmission and Cognitive Processing in Huntington’s Disease

“…This sort of compromised appreciation of elapsed time also seems to present among pre-HD patients (Rowe et al, 2010;Paulsen et al, 2008;Beste et al, 2007). In fact, in an extensive review, Matell and Meck (2004) support the hypothesis that a primary role of the basal ganglia depends on the timing of coincident cortical inputs, and subsequent integration that occurs on MSNs, to generate conscious appreciation of time.…”