Unravelling individual rhythmic abilities using machine learning.

Humans can easily extract the rhythm of a complex sound, like music, and move to its regular beat, like in dance. These abilities are modulated by musical training and vary significantly in untrained individuals. The causes of this variability are multidimensional and typically hard to grasp in single tasks. To date we lack a comprehensive model capturing the rhythmic fingerprints of both musicians and non-musicians. Here we harnessed machine learning to extract a parsimonious model of rhythmic abilities, based on behavioral testing (with perceptual and motor tasks) of individuals with and without formal musical training (n = 79). We demonstrate that variability in rhythmic abilities and their link with formal and informal music experience can be successfully captured by profiles including a minimal set of behavioral measures. These findings highlight that machine learning techniques can be employed successfully to distill profiles of rhythmic abilities, and ultimately shed light on individual variability and its relationship with both formal musical training and informal musical experiences.

Inhalation boosts perceptual awareness and decision speed.

The emergence of consciousness is one of biology's biggest mysteries. During the past two decades, a major effort has been made to identify the neural correlates of consciousness, but in comparison, little is known about the physiological mechanisms underlying first-person subjective experience. Attention is considered the gateway of information to consciousness. Recent work suggests that the breathing phase (i.e., inhalation vs. exhalation) modulates attention, in such a way that attention directed toward exteroceptive information would increase during inhalation. One key hypothesis emerging from this work is that inhalation would improve perceptual awareness and near-threshold decision-making. The present study directly tested this hypothesis. We recorded the breathing rhythms of 30 humans performing a near-threshold decision-making task, in which they had to decide whether a liminal Gabor was tilted to the right or the left (objective decision task) and then to rate their perceptual awareness of the Gabor orientation (subjective decision task). In line with our hypothesis, the data revealed that, relative to exhalation, inhalation improves perceptual awareness and speeds up objective decision-making, without impairing accuracy. Overall, the present study builds on timely questions regarding the physiological mechanisms underlying consciousness and shows that breathing shapes the emergence of subjective experience and decision-making.NEW & NOTEWORTHY Breathing is a ubiquitous biological rhythm in animal life. However, little is known about its effect on consciousness and decision-making. Here, we measured the respiratory rhythm of humans performing a near-threshold discrimination experiment. We show that inhalation, compared with exhalation, improves perceptual awareness and accelerates decision-making while leaving accuracy unaffected.

Impaired Sequential but Preserved Motor Memory Consolidation in Multiple Sclerosis Disease.

Studies investigating motor learning in patients with multiple sclerosis (MS) disease highlighted that MS patients exhibit similar learning performance than healthy controls, but that learning can be hampered by the progression of MS eventually leading to impaired efficiency of subcortical-cortical networks. We aimed at investigating whether the long-term, overnight consolidation of sequential motor memories is preserved in MS disease. Thirty-one patients with MS and two healthy control groups (27 young and 14 middle age) were tested over two consecutive days using a serial reaction time task. Performance was tested (a) 20 min after the end of learning at Day 1 to monitor transient offline, short-term increase in motor and sequential performance and (b) after 24 h on Day 2 to quantify overnight delayed changes in performance reflecting memory consolidation. Besides a slower overall RT in patients with MS, motor performance similarly evolved in all groups. Sequence learning as assessed by interference effects was similar in patients with MS and both control groups on Day 1 (Learning and 20-min test). In contrast, while interference effects keep increasing on Day 2 after 24 h (Relearning) in healthy control groups, it reverted to levels reached at the end of learning for patients with MS. Long-term consolidation of sequential knowledge is impaired in patients with MS. At the motor level, learning and overnight consolidation abilities are preserved in MS disease.

Cognitive task avoidance correlates with fatigue-induced performance decrement but not with subjective fatigue.

Mentally demanding tasks feel effortful and are usually avoided. Furthermore, prolonged cognitive engagement leads to mental fatigue, consisting of subjective feeling of exhaustion and decline in performance. Despite the intuitive characterization of fatigue as an increase in subjective effort perception, the effect of fatigue on effort cost has never been tested experimentally. To this end, sixty participants in 2 separate experiments underwent a forced-choice working memory task following either a fatigue-inducing (i.e. cognitive task involving working memory, conflict and switch costs) or a control manipulation. We measured fatigue in terms of subjective feeling and performance decrement and assessed effort in terms of subjective perception and task avoidance. Subjects exhibited only weak avoidance of the working memory task, with stronger influence of reward than task difficulty on their decisions. In addition, we found that task avoidance did not systematically change following the fatigue manipulation but that variations in task avoidance correlated with fatigue-induced performance decline. The other measures of fatigue and effort were unrelated to each other. Our findings suggest that subjective fatigue may develop independently of task avoidance and suggest an "anticipatory regulation" model in which fatigue urges subjects to stop in anticipation of possible, future adverse consequences.

Locus Coeruleus atrophy doesn't relate to fatigue in Parkinson's disease.

Fatigue is a frequent complaint among healthy population and one of the earliest and most debilitating symptoms in Parkinson's disease (PD). Earlier studies have examined the role of dopamine and serotonin in pathogenesis of fatigue, but the plausible role of noradrenalin (NA) remains underexplored. We investigated the relationship between fatigue in Parkinsonian patients and the extent of degeneration of Locus Coeruleus (LC), the main source of NA in the brain. We quantified LC and Substantia Nigra (SN) atrophy using neuromelanin-sensitive imaging, analyzed with a novel, fully automated algorithm. We also assessed patients' fatigue, depression, sleep disturbance and vigilance. We found that LC degeneration correlated with the levels of depression and vigilance but not with fatigue, while fatigue correlated weakly with atrophy of SN. These results indicate that LC degeneration in Parkinson's disease is unlikely to cause fatigue, but may be involved in mood and vigilance alterations.

Test-retest reliability of the Battery for the Assessment of Auditory Sensorimotor and Timing Abilities (BAASTA).

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.

Gait improvement via rhythmic stimulation in Parkinson's disease is linked to rhythmic skills.

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.

BAASTA: Battery for the Assessment of Auditory Sensorimotor and Timing Abilities.

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.

"Lost in time" but still moving to the beat.

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.

Effects of musically cued gait training in Parkinson's disease: beyond a motor benefit.

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.

Musically cued gait-training improves both perceptual and motor timing in Parkinson's disease.

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.

Role of neuropeptide Y Y1 and Y2 receptors on behavioral despair in a rat model of depression with co-morbid anxiety.

Accumulated evidence suggests that neuropeptide Y (NPY) is involved in emotional disorders by acting on Y(1) and Y(2) receptors. This hypothesis is based on animal studies carried out in naïve normal animals but not in animal models of depression, including the olfactory bulbectomized (OBX) rat. The OBX rat produces a wide array of symptoms that mimic several aspects of human depression and anxiety disorders. In the present study, we aimed to investigate the effects of sustained (2 weeks) intracerebroventricular administration of NPY Y(1) and Y(2) agonists and antagonists in a battery of behavioral tests including the open field, forced swim test (FST) and social interaction (SI) tests in OBX rats. The levels of Y(1) and Y(2) receptors in the hippocampus and basolateral amygdala (BLA) were also evaluated. Treatment with the Y(1)-like receptor agonist, [Leu(31)Pro(34)]PYY, decreased both depressive- and anxiogenic-like behaviors. The Y(2) receptor antagonist, BIIE0246, decreased the immobility time in the FST in OBX animals and increased active contacts in the SI test in sham rats. The Y(2) agonist, PYY3-36, increased the immobility time in the FST in OBX rats. Additionally, increased levels of Y(2) receptor binding were quantified in the dorsal hippocampus and BLA in OBX rats. Taken together, the autoradiographic results add further evidence that the NPYergic system is altered in disturbed emotional states. Moreover, we demonstrate a differential role for NPY Y(1) and Y(2) receptors in emotional processes under control and challenged conditions. This article is part of a Special Issue entitled 'Anxiety and Depression'.

Genomic and proteomic strategies to identify novel targets potentially involved in learning and memory.

The hippocampus is a crucial player across several learning and memory domains, and is highly vulnerable to alterations during aging. Several products of neurotransmitter genes and neuromodulator genes (which play important parts in mediating and maintaining cognitive ability as a function of age) are expressed in hippocampal formation. However, they represent only a small fraction of genes known to be expressed in this region. We review here recent studies on the use of cDNA microarray and proteomic approaches to uncover novel genes and pathways that might be involved in cognitive processes in the aged brain. We and other authors have demonstrated major individual differences in cognitive ability in rats of a similar age, thereby making it possible to directly compare gene products expressed as a function of age and cognitive status. Examples of the possible functional role of some of these genes (e.g. transthyretin, quinone reductase 2) and gene products are discussed.

Loss of quinone reductase 2 function selectively facilitates learning behaviors.

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.