Training based on rhythmic auditory stimulation (RAS) can improve gait in patients with idiopathic Parkinson’s disease (IPD). Patients typically walk faster and exhibit greater stride length after RAS. However, this effect is highly variable among patients, with some exhibiting little or no response to the intervention. These individual differences may depend on patients’ ability to synchronize their movements to a beat. To test this possibility, 14 IPD patients were submitted to RAS for four weeks, in which they walked to music with an embedded metronome. Before and after the training, patients’ synchronization was assessed with auditory paced hand tapping and walking to auditory cues. Patients increased gait speed and stride length in non-cued gait after training. However, individual differences were apparent as some patients showed a positive response to RAS and others, either no response, or a negative response. A positive response to RAS was predicted by the synchronization performance in hand tapping and gait tasks. More severe gait impairment, low synchronization variability, and a prompt response to a stimulation change foster a positive response to RAS training. Thus, sensorimotor timing skills underpinning the synchronization of steps to an auditory cue may allow predicting the success of RAS in IPD.

It is well established that auditory cueing improves gait in patients with idiopathic Parkinson’s disease (IPD). Disease-related reductions in speed and step length can be improved by providing rhythmical auditory cues via a metronome or music. However, effects on cognitive aspects of motor control have yet to be thoroughly investigated. If synchronization of movement to an auditory cue relies on a supramodal timing system involved in perceptual, motor, and sensorimotor integration, auditory cueing can be expected to affect both motor and perceptual timing. Here, we tested this hypothesis by assessing perceptual and motor timing in 15 IPD patients before and after a 4-week music training program with rhythmic auditory cueing. Long-term effects were assessed 1 month after the end of the training. Perceptual and motor timing was evaluated with a battery for the assessment of auditory sensorimotor and timing abilities and compared to that of age-, gender-, and education-matched healthy controls. Prior to training, IPD patients exhibited impaired perceptual and motor timing. Training improved patients’ performance in tasks requiring synchronization with isochronous sequences, and enhanced their ability to adapt to durational changes in a sequence in hand tapping tasks. Benefits of cueing extended to time perception (duration discrimination and detection of misaligned beats in musical excerpts). The current results demonstrate that auditory cueing leads to benefits beyond gait and support the idea that coupling gait to rhythmic auditory cues in IPD patients relies on a neuronal network engaged in both perceptual and motor timing.

The Battery for the Assessment of Auditory Sensorimotor and Timing Abilities (BAASTA) is a new tool for the systematic assessment of perceptual and sensorimotor timing skills. It spans a broad range of timing skills aimed at differentiating individual timing profiles. BAASTA consists of sensitive time perception and production tasks. Perceptual tasks include duration discrimination, anisochrony detection (with tones and music), and a version of the Beat Alignment Task. Perceptual thresholds for duration discrimination and anisochrony detection are estimated with a maximum likelihood procedure (MLP) algorithm. Production tasks use finger tapping and include unpaced and paced tapping (with tones and music), synchronization-continuation, and adaptive tapping to a sequence with a tempo change. BAASTA was tested in a proof-of-concept study with 20 non-musicians (Experiment 1). To validate the results of the MLP procedure, less widespread than standard staircase methods, three perceptual tasks of the battery (duration discrimination, anisochrony detection with tones, and with music) were further tested in a second group of non-musicians using 2 down / 1 up and 3 down / 1 up staircase paradigms (n = 24) (Experiment 2). The results show that the timing profiles provided by BAASTA allow to detect cases of timing/rhythm disorders. In addition, perceptual thresholds yielded by the MLP algorithm, although generally comparable to the results provided by standard staircase, tend to be slightly lower. In sum, BAASTA provides a comprehensive battery to test perceptual and sensorimotor timing skills, and to detect timing/rhythm deficits.

Auditory stimulation via rhythmic cues can be used successfully in the rehabilitation of motor function in patients with motor disorders. A prototypical example is provided by dysfunctional gait in patients with idiopathic Parkinson's disease (PD). Coupling steps to external rhythmic cues (the beat of music or the sounds of a metronome) leads to long-term motor improvements, such as increased walking speed and greater stride length. These effects are likely to be underpinned by compensatory brain mechanisms involving cerebellar-thalamocortical networks. Because these areas are also involved in perceptual and motor timing, parallel improvement in timing tasks is expected in PD beyond purely motor benefits. In keeping with this idea, we report here recent behavioral data showing beneficial effects of musically cued gait training (MCGT) on gait performance (i.e., increased stride length and speed), perceptual timing (e.g., discriminating stimulus durations), and sensorimotor timing abilities (i.e., in paced tapping tasks) in PD patients. Particular attention is paid to individual differences in timing abilities in PD, thus paving the ground for an individualized MCGT-based therapy.

Motor synchronization to the beat of an auditory sequence (e.g., a metronome or music) is widespread in humans. However, some individuals show poor synchronization and impoverished beat perception. This condition, termed "beat deafness", has been linked to a perceptual deficit in beat tracking. Here we present single-case evidence (L.A. and L.C.) that poor beat tracking does not have to entail poor synchronization. In a first Experiment, L.A., L.C., and a third case (L.V.) were submitted to the Battery for The Assessment of Auditory Sensorimotor and Timing Abilities (BAASTA), which includes both perceptual and sensorimotor tasks. Compared to a control group, L.A. and L.C. performed poorly on rhythm perception tasks, such as detecting time shifts in a regular sequence, or estimating whether a metronome is aligned to the beat of the music or not. Yet, they could tap to the beat of the same stimuli. L.V. showed impairments in both beat perception and tapping. In a second Experiment, we tested whether L.A., L.C., and L.V.'s perceptual deficits extend to an implicit timing task, in which they had to respond as fast as possible to a different target pitch after a sequence of standard tones. The three beat-deaf participants benefited similarly to controls from a regular temporal pattern in detecting the pitch target. The fact that synchronization to a beat can occur in the presence of poor perception shows that perception and action can dissociate in explicit timing tasks. Beat tracking afforded by implicit timing mechanisms is likely to support spared synchronization to the beat in some beat-deaf participants. This finding suggests that separate pathways may subserve beat perception depending on the explicit/implicit nature of a task in a sample of beat-deaf participants.

No abstract

High levels of reactive oxygen species (ROS) are associated with deficits in learning and memory with age as well as in Alzheimer's disease. Using DNA microarray, we demonstrated the overexpression of quinone reductase 2 (QR2) in the hippocampus in two models of learning deficits, namely the aged memory impaired rats and the scopolamine-induced amnesia model. QR2 is a cytosolic flavoprotein that catalyzes the reduction of its substrate and enhances the production of damaging activated quinone and ROS. QR2-like immunostaining is enriched in cerebral structures associated with learning behaviors, such as the hippocampal formation and the temporofrontal cortex of rat, mouse, and human brains. In cultured rat embryonic hippocampal neurons, selective inhibitors of QR2, namely S26695 and S29434, protected against menadione-induced cell death by reversing its proapoptotic action. S26695 (8 mg/kg) also significantly inhibited scopolamine-induced amnesia. Interestingly, adult QR2 knock-out mice demonstrated enhanced learning abilities in various tasks, including Morris water maze, object recognition, and rotarod performance test. Other behaviors related to anxiety (elevated plus maze), depression (forced swim), and schizophrenia (prepulse inhibition) were not affected in QR2-deficient mice. Together, these data suggest a role for QR2 in cognitive behaviors with QR2 inhibitors possibly representing a novel therapeutic strategy toward the treatment of learning deficits especially observed in the aged brain.

Perceptual and sensorimotor timing skills can be thoroughly assessed with the Battery for the Assessment of Auditory Sensorimotor and Timing Abilities (BAASTA). The battery has been used for testing rhythmic skills in healthy adults and patient populations (e.g., with Parkinson disease), showing sensitivity to timing and rhythm deficits. Here we assessed the test-retest reliability of the BAASTA in 20 healthy adults. Participants were tested twice with the BAASTA, implemented on a tablet interface, with a 2-week interval. They completed 4 perceptual tasks, namely, duration discrimination, anisochrony detection with tones and music, and the Beat Alignment Test (BAT). Moreover, they completed motor tasks via finger tapping, including unpaced and paced tapping with tones and music, synchronization-continuation, and adaptive tapping to a sequence with a tempo change. Despite high variability among individuals, the results showed good test-retest reliability in most tasks. A slight but significant improvement from test to retest was found in tapping with music, which may reflect a learning effect. In general, the BAASTA was found a reliable tool for evaluating timing and rhythm skills.