A Randomized Clinical Trial of High-Dosage Coenzyme Q10 in Early Parkinson Disease No Evidence of Benefit The Parkinson Study Group QE3 Investigators IMPORTANCE Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit. OBJECTIVE To examine whether CoQ10 could slow disease progression in early PD. DESIGN, SETTING, AND PARTICIPANTS A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation. INTERVENTIONS The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E. MAIN OUTCOMES AND MEASURES Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo. RESULTS The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo). CONCLUSIONS AND RELEVANCE Coenzyme Q10 was safe and well tolerated in this population, bu...

Sorting procedures are frequently adopted as an alternative to dissimilarity ratings to measure the dissimilarity of large sets of stimuli in a comparatively short time. However, systematic empirical research on the consequences of this experimentdesign choice is lacking. We carried out a behavioral experiment to assess the extent to which sorting procedures compare to dissimilarity ratings in terms of efficiency, reliability, and accuracy, and the extent to which data from different data-collection methods are redundant and are better fit by different distance models. Participants estimated the dissimilarity of either semantically charged environmental sounds or semantically neutral synthetic sounds. We considered free and hierarchical sorting and derived indications concerning the properties of constrained and truncated hierarchical sorting methods from hierarchical sorting data. Results show that the higher efficiency of sorting methods comes at a considerable cost in terms of data reliability and accuracy. This loss appears to be minimized with truncated hierarchical sorting methods that start from a relatively low number of groups of stimuli. Finally, variations in data-collection method

A number of psychophysiological measures indexing autonomic and somatovisceral activation to music have been proposed in line with the wider emotion literature. However, attempts to replicate experimental findings and provide converging evidence for music-evoked emotions through physiological changes, overt expression, and subjective measures have had mixed success. This may be due to issues in stimulus and participant selection. Therefore, the aim of Experiment 1 was to select musical stimuli that were controlled for instrumentation, musical form, style, and familiarity. We collected a wide range of subjective responses from 30 highly trained musicians to music varying along the affective dimensions of arousal and valence. Experiment 2 examined a set of psychophysiological correlates of emotion in 20 different musicians by measuring heart rate, skin conductance, and facial electromyography during listening without requiring behavioral reports. [...

Humans have an impressive, automatic capacity for identifying and organizing sounds in their environment. However, little is known about the timescales that sound identification functions on, or the acoustic features that listeners use to identify auditory objects. To better understand the temporal and acoustic dynamics of sound category identification, two go/no-go perceptual gating studies were conducted. Participants heard speech, musical instrument, and human-environmental sounds ranging from 12.5 to 200 ms in duration. Listeners could reliably identify sound categories with just 25 ms of duration. In experiment 1, participants' performance on instrument sounds showed a distinct processing advantage at shorter durations. Experiment 2 revealed that this advantage was largely dependent on regularities in instrument onset characteristics relative to the spectrotemporal complexity of environmental sounds and speech. Models of participant responses indicated that listeners used spectral, temporal, noise, and pitch cues in the task. Aspects of spectral centroid were associated with responses for all categories, while noisiness and spectral flatness were associated with environmental and instrument responses, respectively. Responses for speech and environmental sounds were also associated with spectral features that varied over time. Experiment 2 indicated that variability in fundamental frequency was useful in identifying steady state speech and instrument stimuli.

Human listeners can quickly and easily recognize different sound sources (objects and events) in their environment. Understanding how this impressive ability is accomplished can improve signal processing and machine intelligence applications along with assistive listening technologies. However, it is not clear how the brain represents the many sounds that humans can recognize (such as speech and music) at the level of individual sources, categories and acoustic features. To examine the cortical organization of these representations, we used patterns of fMRI responses to decode 1) four individual speakers and instruments from one another (separately, within each category), 2) the superordinate category labels associated with each stimulus (speech or instrument), and 3) a set of simple synthesized sounds that could be differentiated entirely on their acoustic features. Data were collected using an interleaved silent steady state sequence to increase the temporal signal-to-noise ratio, and mitigate issues with auditory stimulus presentation in fMRI. Largely separable clusters of voxels in the temporal lobes supported the decoding of individual speakers and instruments from other stimuli in the same category. Decoding the superordinate category of each sound was more accurate and involved a larger portion of the temporal lobes. However, these clusters all overlapped with areas that could decode simple, acoustically separable stimuli. Thus, individual sound sources from different sound categories are represented in separate regions of the temporal lobes that are situated within regions implicated in more general acoustic processes. These results bridge an important gap in our understanding of cortical representations of sounds and their acoustics.