Dopamine modulation of motor and implicit learning contributions to auditory temporal attention

Dopamine modulation of motor and implicit learning contributions to auditory temporal attention | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Dopamine modulation of motor and implicit learning contributions to auditory temporal attention Arnaud Zalta, Lena-Franziska Spitz, Prof Alfons Schnitzler, Benjamin Morillon, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7301023/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Auditory periodic temporal attention is a fundamental rhythmic process that operates optimally around 1.5 Hz. Synchronized rhythmic movements further enhance its efficacy. This link between movement and timing is thought to rely on the subcortical basal ganglia dopamine pathway, which is crucial for both motor functions and temporal processing. However, whether dopamine underpins the relationship between auditory temporal attention and motor activity remains unclear. Using an auditory temporal attention task with Parkinsonian patients either ON or OFF the dopaminergic medication L-DOPA and healthy controls, we found that dopamine does not modulate the optimal sampling rate of auditory temporal attention, at 1.5 Hz. However, dopamine enables motor synchronization to the auditory stream and is hence crucial for the motor benefits of auditory temporal attention. Finally, early dopaminergic support is necessary to consolidate performance improvements across sessions. These findings underscore a selective role for dopamine in audio-motor interaction, while suggesting that the intrinsic rhythm of auditory attention is dopamine-independent. Biological sciences/Neuroscience/Cognitive neuroscience/Attention Biological sciences/Psychology/Human behaviour Biological sciences/Neuroscience/Diseases of the nervous system/Parkinson's disease Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction To pay attention in time is essential for capturing relevant information and adapting behaviour to the external world. Temporal attention plays a key role in predicting and adjusting to dynamic external stimuli. However, unlike the continuous flow of sensory input, temporal attention —even though flexible— is constrained and rhythmic, a feature observed both behaviourally and neurophysiologically 1 – 4 . Auditory temporal attention and motor processes share similar temporal constraints, with optimal processing observed at ~ 1.5-2 Hz 1 , 5 – 8 . Engaging in a motor act during an auditory temporal attention task further enhances performance 1 , 9 – 13 . Notably, even in the absence of overt movement, tasks involving temporal prediction or time perception recruit motor cortical areas 9 , 12 , 14 – 16 . However, the precise neural correlates of this audio-motor interaction remain unclear, and whether these shared temporal constraints arise from a common neural substrate has yet to be determined. Dopamine plays a central role in action, motivation, and cognitive functions such as learning and prediction 17 – 20 . The substantia nigra pars compacta, a key dopaminergic structure, contributes to motor control and regulates fine motor skills 21 – 23 . Dopamine is also essential for temporal processing, with the nigrostriatal pathway —including the basal ganglia and striatum— supporting both motor and timing functions 14 , 24 – 26 . Disrupting the midbrain dopaminergic network impairs time estimation 26 – 30 , and dopaminergic antagonists reduce timing accuracy 31 , 32 . In Parkinson’s disease (PD), characterized by the degeneration of dopaminergic neurons, the core symptoms are motor-related, including akinesia, tremor, and bradykinesia 33 , 34 . Fine motor skills are also impaired in this pathology independently of this classical symptomatology 34 , 35 . However, beyond these motor deficits, cognitive symptoms such as disruptions in decision-making, goal-directed behaviour 36 , 37 and time perception 38 – 43 are reported. Mild cognitive impairment in Parkinson’s patients is well documented and affects a broad range of functions, including learning and attention 34 , 44 – 48 . Although both motor and cognitive symptoms are prominent in Parkinson’s disease, their relationship remains complex and not fully understood. Some studies report correlations between the severity of motor symptoms and the extent of cognitive decline and even identify potential neurophysiological markers of this association. Nevertheless, it remains unclear whether motor deficits directly contribute to cognitive deterioration 49 – 52 . To examine how periodic auditory temporal attention interacts with motor function and dopaminergic modulation, we tested PD patients both ON and OFF dopaminergic medication L-DOPA, alongside age-matched healthy controls. Participants performed an auditory temporal attention task under two conditions: passive listening and active motor tracking 1 . In the passive condition, all groups exhibited comparable performance accuracy and shared the same optimal sampling rate, suggesting that internal temporal attention constraints remain preserved despite dopamine depletion. In contrast, motor tracking enhanced performance in healthy controls and PD patients when ON-DOPA, but not when OFF-DOPA, indicating that dopamine is necessary for motor-related performance gains. Finally, administering L-DOPA during a first session led to improved performance in a subsequent OFF-medication session, whereas starting OFF-medication did not produce such gains. These findings indicate that dopamine is not only essential for motor facilitation during auditory temporal attention but also plays a critical role in enabling learning across sessions. Materials & methods Participants. 26 parkinsonian patients (age mean: 66.5 years; age range: 54–80 years; 24% of females) and 20 healthy age-matched participants (age mean: 64.8 years; age range: 52–86 years; 20% of females) were recruited. Finally, nine Parkinsonian patients were excluded from the analysis because they did not complete the experiment. To view the details of the population, please refer to Table 1 . The experiment followed the local ethics guidelines from Heinrich Heine University, Düsseldorf and was approved by the local ethics committee (study-no: 2019 − 488_1). Informed consent was obtained from all participants before the experiments. All healthy participants had normal audition and vision and reported no history of neurological or psychiatric disorders. We did not select participants based on musical training and a short survey made at the end of the experiment informed us that none of them were professional musicians. Table 1 Demographic and clinical characteristics of the PD patients. m: male, f: female; BDI: Beck Depression Inventory; MDRS: Mattis Dementia Rating Scale; MDS-UPDRS 3: Unified Parkinson’s Disease Rating Scale; ON: under dopaminergic (L-dopa) medication; OFF: not under dopaminergic (L-dopa); Parkinson’s patients: Parkinson disease. Patient gender Age (years) BDI MDRS Duration between initial diagnosis and experiment (years) MDS-UPDRS ON MDS-UPDRS OFF Challenge Dose of L-Dopa (mg) State condition 1/2 TYPE OF PD 1 m 80 8 140 15 31 45 200 ON/OFF tremor-dominant 2 m 65 20 137 4 10 26 250 ON/OFF equivalent 3 m 67 5 139 9 4 17 150 ON/OFF equivalent 4 m 60 14 141 11 24 30 300 ON/OFF equivalent 5 m 77 14 141 15 22 38 75 OFF/ON (akinetic-rigid) 6 m 66 4 135 10 3 11 200 OFF/ON akinetic-rigid 7 m 61 8 142 4 17 29 300 OFF/ON equivalent 8 m 62 13 138 13 10 39 200 OFF/ON equivalent 9 m 69 9 135 6 31 45 300 ON/OFF equivalent 10 f 56 0 142 7 34 50 150 ON/OFF equivalent 11 m 67 14 139 4 21 22 100 OFF/ON tremor-dominant 12 m 72 9 139 10 13 24 200 OFF/ON equivalent 13 m 72 7 137 13 28 35 250 OFF/ON akinetic-rigid 14 m 73 1 143 6 7 17 250 OFF/ON equivalent 15 f 73 9 139 14 46 63 250 ON/OFF akinetic-rigid 16 m 54 23 142 4 44 45 100 OFF/ON equivalent 17 f 59 15 137 12 25 45 150 ON/OFF equivalent 18 f 64 6 139 5 15 28 150 OFF/ON equivalent 19 f 58 6 136 1 20 26 100 OFF/ON hypokinetic-rigid 20 f 69 17 131 11 24 30 100 ON/OFF equivalent 21 f 68 14 135 13 42 60 200 ON/OFF hypokinetic-rigid 22 f 75 26 124 10 38 55 150 ON/OFF hypokinetic-rigid 23 m 70 5 137 10 17 35 75 ON/OFF hypokinetic-rigid 24 m 59 16 140 3 26 38 200 ON/OFF tremor-dominant 25 m 57 25 132 6 15 36 200 ON/OFF tremor-dominant 26 m 63 6 137 10 15 43 100 ON/OFF hypokinetic-rigid Average 66,00 11,3 137,6 8,7 22,4 35,8 180,8 Experimental design. The experiment was adapted from 1 . Auditory stimuli were sampled at 44 100 Hz and presented binaurally at a comfortable hearing level via headphones in a quiet room, using the Psychophysics-3 toolbox 78 and additional custom scripts written for MATLAB (The Mathworks). The instructions were displayed visually on a mid-grey background of a laptop screen situated at a viewing distance of 50 cm. The screen had a spatial resolution of 1920 by 1080 pixels and a vertical refresh rate of 60 Hz. On each trial, participants had to fixate a cross, located at the centre of the screen, to get a constant visual stimulation. Each trial consisted of a sequence of pure tones, qualified as reference, targets, and distractors (Fig. 1 a). Three reference tones defining the beat of the sequence preceded a mixture of on-beat (target) and off-beat (distractor) tones. Participants performed a beat discrimination task at the end of each trial, by deciding whether the last tone of the sequence, a spectral deviant (785 Hz vs. 660 Hz), was on or off beat. While on-beat stimuli were providing the beat, crucially, off-beat stimuli had a distracting influence. This interleaved delivery of sensory events forced participants to track the beat throughout the entire duration of the sequence while minimising the interference of aperiodic events. This protocol thus ensured that their attentional focus was temporally modulated over an extended time period. This design implies that the last inter-stimulus interval (ISI) did not always correspond to the beat period of the trial. Distractors could occur between the last target tone and the deviant. Tone frequencies were selected to avoid potential bone transmission (660/785 Hz). 4 beat frequencies (or tempi) of 0.6, 1.5, 2.2, and 3.5 Hz were presented to the participant to span the entire range of discernible beats 53 , 54 . We orthogonalized tempi and tone duration by fixing tone duration to 22.5 ms. Tones dampening length was 10% of their duration, and tone attenuation was 40 dB. Trials had pseudo-random durations (~ 2–12 s) but included in each tempo at least four targets (and up to 22; reference tones and deviant excluded) and lasted at least 2 s. These constraints were chosen to enable the deployment of temporal attention in all tempi. The density of distractors per sequence (i.e., the number of distractors per beat) was titrated individually (see below). Distractors appeared randomly between targets, with the constraint that all ISI within the sequence should be of at least 9% of the beat period (e.g., ISI > 90 ms for a 1 Hz beat). This ensured that tones did not appear concomitantly. The deviant target was occurring either on or off beat (50/50%). When the deviant was off beat, it appeared randomly within a window corresponding to one beat period and centred around the expected beat. Participants performed ‘passive’ blocks, in which they executed the task while staying completely still during the duration of the trial, not moving any part of their body. Additionally, participants performed ‘tracking’ blocks, in which they were required to follow the beat by moving their (left or right, at their convenience) index finger, on a noiseless pad or on a key of the experiment’s laptop keyboard, from the beginning of the sequence (the 2nd reference tone). In essence, the tracking condition is a variation of the synchronisation-continuation paradigm 6 . For PD patients, two passive and tracking conditions were performed, one with (ON) and one without (OFF) L-DOPA medication. For the OFF-L-DOPA state, patients were recorded in the clinically defined medication OFF state following withdrawal of dopaminergic medication overnight for at least 12 hours prior to study completion. For the ON L-DOPA state, patients were measured in their best clinical ON state. The ON- and OFF-DOPA states occurred on different days, if the ON measurement was performed first. Otherwise, the ON measurement was made after the OFF-state measurement and at least 30 minutes after the intake of up to 1.5 times their morning L-DOPA dosage in the form of a fast-acting dopamine. Each participant started the experiment with a short training block. The beat frequency was fixed to 2 Hz, and the density of distractors was at first equal to zero and increased progressively up to 0.4 distractors per beat. Participants were instructed not to move during the trials (as in the passive condition). Then, participants listened to the 4 tempi at least 1 time each. Following this short training block, participants performed a psychophysical staircase where the density of distractors was the varying parameter. The staircase was set to obtain ~ 75% of categorisation performance. Participants performed 40 trials per tempo per condition. Tempi were pseudo-randomly alternating in blocks of 20 trials, each with or without tracking demand. Feedback was provided after each trial to indicate correct/incorrect responses, and more general performance feedback, indicating the total number of correct responses was given after every block, for motivational purposes. Trials with outlier reaction times (more than two standard deviations away from the mean per participant, condition, and tempo) were excluded. Timing of motor acts in the tracking condition. To investigate the ability of participants to actively follow the beat, we extracted the timing of individual motor acts in the tracking condition. For each trial, we computed the standard deviation of the inter-tap intervals. Estimation of an optimal beat frequency. To estimate the tempo at which performance would be maximal (/minimal), variations of performance across tempi were approximated at the individual level with a third-order polynomial function f(x) = ax 3 + bx 2 + cx + d, and the coordinates of the local maxima α (/minima β) were extracted according to the functions: $$\:{\alpha\:}=\frac{-b-\sqrt{{\delta\:}}}{3a};{\beta\:}=\frac{-b+\sqrt{{\delta\:}}}{3a}$$ where \(\:\delta\:={b}^{2}-3ac\) with δ > 0. We used a third-order polynomial function, as it is the best (i.e. most flexible) model that allows estimating one maximum without ambiguity (higher order models accept multiple maxima). A second-order function was used for visualisation purposes when fitting the group-level performance profile. Statistical procedures . All analyses were performed at the single-subject level and followed by standard non-parametric two-sided tests at the group level (Wilcoxon paired signed-rank, unpaired Mann-Whitney or Friedman tests). The divergence in participants' tapping from the tempo of the presented sequences was calculated using the norm of the difference between their tapping frequency and the beat frequency. Results Parkinson’s disease does not affect auditory temporal attention capacities. Sequences of pure tones were presented on each trial, from 2 to ~ 20 s. Three reference stimuli defining the tempo (or beat frequency) of the isochronous event sequence preceded a mixture of on-beat and off-beat stimuli. Participants performed a beat discrimination task at the end of each trial, by deciding whether the last stimulus of the sequence, a deviant, was on or off beat (Fig. 1 a). While on-beat stimuli were reinforcing the beat, crucially, off-beat stimuli had a distracting influence. This interleaved delivery of sensory events forced participants to track the beat throughout the entire duration of the sequence while minimising the interference of aperiodic distractors. This protocol ensures that participant’s attentional focus is temporally modulated over an extended time period. The density of distractors (i.e., number of distractors per beat) was titrated for each participant prior to the experiment to reach threshold performance for a 2 Hz tempo (see Methods). Four tempi were then investigated, with isochronous tempi of 0.6, 1.5, 2.2, and 3.5 Hz, to span most of the range of discernible tempi 53 , 54 . Participants completed two conditions in this task. A passive condition, in which they performed the task while staying completely still throughout each trial. Participants performed also a tracking condition, in which they tapped the beat in phase, with their index finger (see methods). Therefore, the absence or presence of overt movement was the single difference between the two conditions. While it is not possible to control for the covert involvement of motor and/or premotor structures during temporal attention tasks, comparing passive and tracking conditions allows us to quantify the influence of overt (relative to covert) motor activity on the precision of temporal attention. To investigate whether dopamine dysfunction impacts auditory periodic temporal attention, PD patients and age-matched healthy participants performed the same experiment. The average difficulty level (density of distractors) estimated during a staircase titration procedure was around 0.6 for the two groups (controls: M = 0.69, SD = 0.63; Parkinson’s patients: M = 0.49, SD = 0.22; Fig. 1 b) and did not significantly differ across groups (unpaired Mann-Whitney test: U = 159, p = 0.73, r = 0.06, Bayes Factor (BF) = 0.57). Moreover, during the main experiment, the two groups did not differ significantly in performance accuracy (% correct responses) across tempi and conditions (mean controls = 0.70; mean Parkinson’s patients = 0.69; Friedman test, main effect of performance: U = 161, p = 0.80, r = 0.04, BF = 0.33). Age and dopamine modulation do not affect the optimal rate of auditory temporal attention. We then investigated whether dopamine modulation affects the optimal rate of auditory temporal attention in this task. First, performance varied significantly with tempo across all conditions (listening and tracking), participant groups (controls and PD patients), and sessions (ON and OFF DOPA; Friedman tests: all χ2(3) > 19, all p < 0.001). This notably generalizes our previous result in an elderly population, that auditory periodic temporal attention is rate-restricted 1 . Then, for each condition (passive and tracking) and group (healthy controls and PD patients), the optimal rate was estimated by fitting participants’ accuracy across tempi (see Methods). The optimal beat frequency estimated with individual fits was around 1.5 Hz in both conditions and groups (Fig. 1 c) and did not differ significantly across conditions (passive vs. tracking: controls: Wilcoxon test: Z = 0.45, p = 0.65, BF = 0.43; parkinsonian patients: Z = 0.69, p = 0.49, BF = 0.39) nor across groups (Mann-Whitney test: U = 140, p = 0.37, r = 0.15, BF = 0.49). Overall, these results confirm previous findings that periodic auditory temporal attention is rate-restricted and optimal around 1.5 Hz 1 . To investigate whether L-DOPA medication has an impact on the auditory temporal attention capacities of PD patients, we made the distinction between sessions where patients were ON- or OFF-DOPA medication. We first observed that the optimal beat frequency estimated with individual fits was around 1.5 Hz in all (ON- or OFF-DOPA and listen or tracking condition) sessions and did not differ significantly across them (Friedman test: χ2(3) = 0.48, p = 0.9; supplementary Fig. 1a). Dopamine modulation of motor contribution to auditory temporal attention. We then investigated whether motor activity helps synchronise temporal fluctuations of attention with the timing of events in a task-relevant stream by comparing the passive and tracking conditions in both healthy controls and PD patients. We observed a significant increase in performance accuracy during motor-tracking compared to passive listening conditions, across groups of participants and tempi (Wilcoxon paired signed-rank test: Z = 3.63, p < 0.001). For PD patients, when ON-DOPA, we observed such a significant increase in performance accuracy (Wilcoxon test: Z = 2.53, p = 0.011; Fig. 2 a & supplementary Fig. 1b), but this was not the case when the same patients performed the same experiment OFF-DOPA (Wilcoxon test: Z = 0.26, p = 0.80, BF = 0.33; Fig. 2 a & supplementary Fig. 1c). The difference in motor benefit across ON- and OFF-DOPA state was significant (Wilcoxon test: Z = 2.20, p = 0.028; Fig. 2 a). More precisely, post-hoc tests indicated that overt motor tracking significantly increased performance when healthy control participants performed the task between 0.6 and 2.2 Hz (Wilcoxon tests: 0.6 Hz: Z = 3.00, p = 0.003; 1.5 Hz: Z = 2.41, p = 0.016; 2.2 Hz: Z = 3.79, p < 0.001; 3.5 Hz: Z = 0.15, p = 0.88, BF = 0.24; Fig. 2 b). The motor benefit was maximal at 2.2 Hz, replicating previous findings 1 . For PD patients in the ON-DOPA state, this motor benefit was also maximal and significant at 2.2 Hz (Wilcoxon test: Z = 3.30, p = 0.001; other tempi: all Z 0.08 all BF < 0.56; Fig. 2 c). We finally tested whether the motor benefit observed in PD patients in the ON-DOPA state correlated with their L-DOPA challenge dosage and MDS-Unified Parkinson's Disease Rating Scale (UPDRS) part 3 scores were assessed during the experimental session. To note, the MDS-UPDRS part 3 score measures the severity of PD by rating motor symptoms across multiple domains. Higher scores indicate more severe impairment 55 . There was a significant negative correlation between motor benefit and L-DOPA dosage (Pearson correlation, r (15) = − 0.50, p = 0.04), indicating that higher doses were associated with reduced motor benefit. In contrast, no significant correlation was found between motor benefit and MDS-UPDRS scores (Pearson correlation, r (15) = 0.12, p = 0.66). Dopamine contribution to motor adaptation. We next investigated participants’ ability to adapt their motor acts to the tempo of the auditory stream by comparing the tempo of their tapping movements to that of the concurrently presented rhythm. We computed the tapping divergence—the deviation between the presented and reproduced tempi (see Methods)—and compared it between groups and sessions. Patients in the ON-DOPA state were able to match the presented tempi similarly to healthy controls (Wilcoxon signed-rank test: z = 0.46, p = 0.64, BF = 0.34; Fig. 3 a, b &c). In contrast, in the OFF-DOPA state, patients showed a clear difficulty in adapting their movements to the tempo of the external auditory stimulus. We found a significant divergence from the tapping frequency of both healthy controls (Wilcoxon signed-rank test: z = − 3.59, p < 0.001; Fig. 3 d) and the same patients in the ON-DOPA state (One sample t test: t = -5.88, p < 0.001). Patients in the OFF-DOPA state tapped essentially at a frequency of around 1.5 Hz, independently of the stimulus tempo. In other words, at tempos above and below 1.5 Hz, they were unable to adapt their tapping speed to the stimulus. Dopamine contribution to implicit learning. Finally, we examined whether the order in which PD patients performed the task —first ON-DOPA then OFF-DOPA, or the reverse— had any effect on the results. Our rationale was that learning effects often occur across repeated sessions of the same task, and L-DOPA intake during the first participation could positively modulate this effect. Parkinson’s patients were therefore divided into two groups: those who began in the ON-DOPA state (n = 8; and performed the second session OFF-DOPA) and those who started in the OFF-DOPA state (n = 9; and performed the second session ON-DOPA). We calculated the change in overall performance (across tempi) between the first and second session to assess learning and the potential influence of medication. We observed a significant learning effect in both passive and tracking conditions for patients who began ON-DOPA (Wilcoxon tests: passive: Z = 2.52, p = 0.012; tracking: Z = 2.38, p = 0.017). In contrast, we didn’t find any learning effect in patients who started OFF-DOPA (passive: Z = 0.06, p = 0.95, BF = 0.23; tracking: Z = 1.48, p = 0.14, BF = 0.89). This learning effect was similar between the passive and tracking conditions (Wilcoxon tests, passive vs. tracking conditions: ON-DOPA first: Z = 1.68, p = 0.09, BF = 0.40; OFF-DOPA first: Z = 1.36, p = 0.17, BF = 0.63) and significantly different in the ON-DOPA-first group compared to the OFF-DOPA-first group (Wilcoxon rank sum test: W = 100, p = 0.006 ; Fig. 4 ). These results suggest that learning across sessions in this task is modulated by L-DOPA intake in PD patients. Discussion How does dopamine affect the audio-motor synergy in periodic temporal attention? Here we extend our understanding of the behavioural and neurophysiological bases of audio-motor interaction by demonstrating that: (1) dopamine does not modulate the intrinsic rhythm of auditory temporal attention (Fig. 1 c); (2) L-DOPA restores the synergy between auditory temporal attention and motor acts in patients with Parkinson’s disease (Fig. 2 ); (3) Dopamine affects fine motor performance: PD patients in the ON-DOPA state synchronize their motor acts with auditory stimuli like healthy controls, unlike in the OFF-DOPA state (Fig. 3 ); (4) Dopamine promotes implicit learning: only PD patients ON-DOPA state during the first session showed a learning effect across sessions in our task (Fig. 4 ). These results extend previous studies on the relationship between dopamine, motor acts, time estimation, and attention 25 , 26 , 32 , 56 , by showing that cortical areas classically associated with motor control are also engaged in timing and temporal prediction functions 16 , 57 , 58 . Some models specifically linked the basal ganglia and dopaminergic pathways with the motor cortical area as part of the time estimation mechanism 14 . Using PD patients as a model of dopamine depletion, we found that the perceptual benefit of overt motor activity disappears when dopamine is lacking during our temporal attentional task. In contrast, in healthy controls or PD patients in the ON-DOPA state, overtly tracking the beat during the experiment enhances performance 1 , 10 . Dopamine, thus, could be crucial for the interactions between motor processes and high cognitive functions such as auditory temporal attention. Coupled oscillator models have been used to describe how synchronization between these systems can emerge, suggesting that motor-attention synergy may underlie the observed effects 1 . Supporting this, coherence analysis in PD patients show that dopamine enhances cortical and muscular connectivity during bilateral gait control 59 . Reduced connectivity between attention and sensorimotor networks has also been associated with mild cognitive impairment in PD patients 60 . However, further investigation is needed to address this question, as our study cannot disentangle the motor disruption effect from the potential role of dopamine in audio-motor connectivity. We didn’t find a difference in task difficulty between PD patients and healthy controls. This may reflect preserved attentional capacities in PD patients, particularly when symptoms are chronically managed with L-DOPA, as suggested by some studies, despite reports of broader cognitive impairments 61 – 64 . One possible explanation for the overall lack of difference in attentional performance between ON and OFF L-DOPA states is that chronic L-DOPA treatment may balance the synaptic degradation typically seen in Parkinson’s disease 34 . Dopamine has been shown to support synaptic maintenance and regeneration, helping to preserve connectivity 65 , 66 . Moreover, our results show that dopamine does not affect the intrinsic frequency of temporal attention but specifically enables motor-driven performance gains. Dopamine could be a key modulator not only of the motor processes but also of the connectivity between motor and cognitive processes. Interestingly, the reported ability to use the auditory rhythm in combination with the motor act to improve perception aligns with studies reporting gait improvement with auditory stimulation, suggesting its perceptual and motor benefit in a Parkinson’s population 67 – 73 . This mechanism likely fails in PD patients due to motor symptoms 33 , 34 that impair their ability to move in phase with attentional dynamics. This interpretation is supported by the increased tapping divergence observed in PD patients in the OFF-DOPA state. A similar absence of modulation has been reported when motor tracking is deliberately decoupled from attention 10 . Biologically, the motor recovery observed with L-DOPA may result from an acute effect driven by increased dopamine levels. But further studies are needed to disentangle the chronic effects from the acute motor benefits of L-DOPA. Of note, we found no correlation between clinical scores, such as the MDS-UPDRS part 3, and the tracking benefit observed in the task. Instead, the behavioural metric correlated negatively only with L-DOPA challenge dosage, which is expected since medication levels typically increase with symptom severity. The absence of a link between clinical and behavioural measures suggests that our task captures motor-cognitive interactions not reflected in standard clinical assessments. However, given our relatively small sample size, these correlations (or the absence of them) should be interpreted with caution. A larger sample is needed to robustly test clinical hypotheses. Nonetheless, our findings highlight the potential of this task to isolate specific motor-attention processes that warrant further investigation. Finally, PD patients OFF-DOPA state during their first experimental participation showed no learning benefit in the second participation (Fig. 4 ). In contrast, when PD patients performed the task first ON-DOPA state, a learning effect was observed, indicating that training could improve performance. These results also support the presence of implicit learning deficits in PD patients, a finding that has been debated in the literature 74 , 75 . A limitation of the study is that PD patients who first performed the task in the ON-DOPA state completed the second session the following day, while those who started in the OFF-DOPA state performed both sessions on the same day. Since sleep can also positively influence learning 76 , 77 , further investigation is needed to clarify whether the observed learning effect stems from dopaminergic modulation, sleep-related consolidation, or both —especially given that our results are consistent with all these explanations. Conclusion In sum, our results indicate that the dopaminergic system is not essential for auditory periodic temporal attention itself but plays a key role in modulating the motor contribution to auditory attention and in learning within this task. Dopamine thus appears crucial for regulating motor and learning processes and their interaction with cognitive functions such as auditory perception and temporal attention. Declarations Data Availability Statement. The data reported in this paper, along with the analysis pipelines, can be accessed upon request from the corresponding author. Funding and Disclosure. AZ is supported by the Fondation pour la Recherche Médicale (FRM) (SPF202209015740). B.M. has received funding from the European Research Council (ERC, SPEEDY, ERC-CoG-101043344). The authors have nothing to disclose. Acknowledgement. We thank all the patients and healthy participants for their participation. Author Contributions. Conceptualization: B.M., E.F. & A.Z. Data collection: E.F. & L.S. Methodology: B.M. & A.Z. Investigation: B.M. & A.Z. Visualization: A.Z. Funding acquisition: B.M, E.F. & A.S. Project administration: B.M., E.F. and A.Z. Supervision: B.M. and E.F. Writing—original draft: A.Z. Writing—review and editing: all the authors. References Zalta, A., Petkoski, S. & Morillon, B. Natural rhythms of periodic temporal attention. Nat. Commun. 11 , 1–12 (2020). Helfrich, R. F. et al. Neural Mechanisms. Neuron 99 , 854-865.e5 (2018). Fiebelkorn, I. C. & Kastner, S. A Rhythmic Theory of Attention. Trends Cogn. Sci. 23 , 87–101 (2019). Re, D., Inbar, M., Richter, C. G. & Landau, A. N. Feature-Based Attention Samples Stimuli Report Feature-Based Attention Samples Stimuli Rhythmically. Curr. Biol. 1–7 (2019) doi:10.1016/j.cub.2019.01.010. MacDougall, H. G. & Moore, T. S. Marching to the beat of the same drummer: the spontaneous tempo of human locomotion. J. Appl. Physiol. 99 , 1164–1173 (2005). Repp, B. H. & Su, Y. Sensorimotor synchronization : A review of recent research ( 2006 – 2012 ). (2013) doi:10.3758/s13423-012-0371-2. Morillon, B., Arnal, L. H., Schroeder, C. E. & Keitel, A. Prominence of delta oscillatory rhythms in the motor cortex and their relevance for auditory and speech perception. Neurosci. Biobehav. Rev. 107 , 136–142 (2019). Gupta, A., Matthews, T. E., Penhune, V. B. & Morillon, B. Behavioral Evidence for Two Modes of Attention. bioRxiv 2024.09.12.612641 (2024) doi:10.1101/2024.09.12.612641. Morillon, B. & Baillet, S. Motor origin of temporal predictions in auditory attention. Proc. Natl. Acad. Sci. 114 , E8913–E8921 (2017). Morillon, B., Schroeder, C. E. & Wyart, V. Motor contributions to the temporal precision of auditory attention. Nat. Commun. 5 , 1–9 (2014). Te Rietmolen, N., Strijkers, K. & Morillon, B. Moving rhythmically can facilitate naturalistic speech perception in a noisy environment. Proc. B 292 , (2025). De Kock, R., Gladhill, K. A., Ali, M. N., Joiner, W. M. & Wiener, M. How movements shape the perception of time. Trends Cogn. Sci. 25 , 950–963 (2021). Schmidt-Kassow, M., Heinemann, L. V, Abel, C. & Kaiser, J. Auditory-motor synchronization facilitates attention allocation. Neuroimage 82 , 101–106 (2013). Cannon, J. J. & Patel, A. D. How Beat Perception Co-opts Motor Neurophysiology. Trends Cogn. Sci. 25 , 137–150 (2021). Coull, J. T. Functional Anatomy of the Attentional Modulation of Time Estimation. Science (80-. ). 303 , 1506–1508 (2004). Zalta, A., Large, E. W., Schön, D. & Morillon, B. Neural dynamics of predictive timing and motor engagement in music listening. Sci. Adv. 10 , 2525 (2024). Thiele, A. & Bellgrove, M. A. Neuromodulation of Attention. Neuron 97 , 769–785 (2018). Schultz, W., Dayan, P. & Montague, P. R. A neural substrate of prediction and reward. Science (80-. ). 275 , 1593–1599 (1997). Schultz, W. Dopamine reward prediction-error signalling: a two-component response. Nat. Rev. Neurosci. 2016 173 17 , 183–195 (2016). Berke, J. D. What does dopamine mean? Nat. Neurosci. 21 , 787–793 (2018). Bova, A. et al. Precisely-timed dopamine signals establish distinct kinematic representations of skilled movements. Elife 9 , 1–141 (2020). Hunter, J., Bova, A., Stevens, A. & Leventhal, D. K. Dopamine neuron stimulation induces context-dependent abnormal involuntary movements in healthy rats. ISCIENCE 25 , 103974 (2022). Phillips, C. D., Hodge, A. T., Myers, C. C., Leventhal, D. K. & Burgess, C. R. Striatal Dopamine Contributions to Skilled Motor Learning. (2024) doi:10.1523/JNEUROSCI.0240-24.2024. Jones, C. R. G., Malone, T. J. L., Dirnberger, G., Edwards, M. & Jahanshahi, M. Basal ganglia, dopamine and temporal processing: Performance on three timing tasks on and off medication in Parkinson’s disease. (2008) doi:10.1016/j.bandc.2008.02.121. Buhusi, C. V. & Meck, W. H. What makes us tick? Functional and neural mechanisms of interval timing. Nat. Rev. Neurosci. 6 , 755–765 (2005). Breska, A. & Ivry, R. B. Double dissociation of single-interval and rhythmic temporal prediction in cerebellar degeneration and Parkinson’s disease. Proc. Natl. Acad. Sci. U. S. A. 115 , 12283–12288 (2018). Soares, S., Atallah, B. V. & Paton, J. J. Midbrain dopamine neurons control judgment of time. Science (80-. ). 354 , 1273–1277 (2016). Pastor, M. A., Artieda, J., Jahanshahi, M. & Obeso, J. A. Time estimation and reproduction is abnormal in parkinson’s disease. Brain 115 , 211–225 (1992). Honma, M. et al. Impaired cognitive modification for estimating time duration in Parkinson’s disease. PLoS One 13 , e0208956 (2018). Magalhães, F. et al. Neurochemical changes in basal ganglia affect time perception in parkinsonians. J. Biomed. Sci. 2018 251 25 , 1–15 (2018). Coull, J. T., Hwang, H. J., Leyton, M. & Dagher, A. Dopamine precursor depletion impairs timing in healthy volunteers by attenuating activity in putamen and supplementary motor area. J. Neurosci. 32 , 16704–16715 (2012). Tomassini, A., Ruge, D., Galea, J. M., Penny, W. & Bestmann, S. The Role of Dopamine in Temporal Uncertainty. J. Cogn. Neurosci. 26 , 194–198 (2016). Tanner, C. M. & Ostrem, J. L. Parkinson’s Disease. N. Engl. J. Med. 391 , 442–452 (2024). Poewe, W. et al. Parkinson disease. Nat. Rev. Dis. Prim. 3 , 1–21 (2017). Ruitenberg, M. F. L., Duthoo, W., Santens, P., Notebaert, W. & Abrahamse, E. L. Sequential movement skill in Parkinson’s disease: A state-of-the-art. Cortex 102–112 (2015) doi:10.1016/j.cortex.2015.01.005. Colautti, L., Iannello, P., Silveri, M. C. & Antonietti, A. Decision making in Parkinson’s disease: An analysis of the studies using the Iowa Gambling Task. Eur. J. Neurosci. 54 , 7513–7549 (2021). Le Heron, C., Morris, L.-A. & Manohar, S. Understanding disrupted motivation in Parkinson’s disease through a value-based decision-making lens. Trends Neurosci. 48 , (2025). Singh, A. et al. Timing variability and midfrontal ~4 Hz rhythms correlate with cognition in Parkinson’s disease. npj Park. Dis. 7 , 1–8 (2021). Artieda, J., Pastor, M. A., Lacruz, F. & Obeso, J. A. Temporal discrimination is abnormal in parkinson’s disease. Brain 115 , 199–210 (1992). O’Boyle, D. J., Freeman, J. S. & Cody, F. W. J. The accuracy and precision of timing of self-paced, repetitive movements in subjects with Parkinson’s disease. Brain 119 , 51–70 (1996). Malapani, C. et al. Coupled Temporal Memories in Parkinson’s Disease: A Dopamine-Related Dysfunction. J. Cogn. Neurosci. 10 , 316–331 (1998). Malapani, C., Deweer, B. & Gibbon, J. Separating storage from retrieval dysfunction of temporal memory in Parkinson’s disease. J. Cogn. Neurosci. 14 , 311–322 (2002). Merchant, H., Zarco, W., Bartolo, R. & Prado, L. The Context of Temporal Processing Is Represented in the Multidimensional Relationships between Timing Tasks. PLoS One 3 , e3169 (2008). Brown, R. G. & Marsden, C. D. Cognitive function in Parkinson’s disease: From description to theory. Trends Neurosci. 13 , 21–29 (1990). Kehagia, A. A., Barker, R. A. & Robbins, T. W. Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson’s disease. Lancet Neurol. 9 , 1200–1213 (2010). Robbins, T. W. & Cools, R. Cognitive deficits in Parkinson’s disease: A cognitive neuroscience perspective. Mov. Disord. 29 , 597–607 (2014). Bowes, S. G., O’nell, C. J. A., Dobbs, R. J., Dobrs, S. M. & Charlett, A. Bradyphrenia and Parkinsonism. Age Ageing 23 , 1–2 (1994). Severiano e Sousa, C. et al. Profile of cognitive impairment in late-stage Parkinson’s disease. Brain Behav. 12 , (2022). Wang, Y. X. et al. Associations between cognitive impairment and motor dysfunction in Parkinson’s disease. Brain Behav. 7 , e00719 (2017). Pereiro, A. X., Resuá, B., Facal, D. & Cancela-Carral, J. M. Combining a Cognitive Concurrent Task with a Motor or Motor-Cognitive Task: Which Is Better to Differentiate Levels of Affectation in Parkinson’s Disease? Park. Dis. 2020 , 2189084 (2020). Kann, S. J., Chang, C., Manza, P. & Leung, H. C. Akinetic rigid symptoms are associated with decline in a cortical motor network in Parkinson’s disease. npj Park. Dis. 2020 61 6 , 1–8 (2020). Aarsland, D. et al. Parkinson disease-associated cognitive impairment. Nat. Rev. Dis. Prim. 2021 71 7 , 1–21 (2021). Fraisse, P. Rhythm and tempo. in The Psychology of Music (ed. Academic, D. D. N. Y.) 149–180 (1982). Woodrow, H. Time Perception. A Handb. Exp. Psychol. (1951). Goetz, C. C. The Unified Parkinson’s Disease Rating Scale (UPDRS): Status and recommendations. Mov. Disord. 18 , 738–750 (2003). Coull, J. T. Neural correlates of attention and arousal: insights from electrophysiology, functional neuroimaging and psychopharmacology. Prog. Neurobiol. Vol. 55 , (1998). Coull, J., Charras, P., Donadieu, M., Droit-Volet, S. & Vidal, F. SMA Selectively Codes the Active Accumulation of Temporal, Not Spatial, Magnitude. J Cogn Neurosci. 10 , 431–441 (2015). Coull, J. T., Vidal, F. & Burle, B. When to act, or not to act: That’s the SMA’s question. Curr. Opin. Behav. Sci. 8 , 14–21 (2016). Santos, P. C. R. dos, Heimler, B., Koren, O., Flash, T. & Plotnik, M. Dopamine improves defective cortical and muscular connectivity during bilateral control of gait in Parkinson’s disease. Commun. Biol. 7 , 1–15 (2024). Delgado-Alvarado, M., Ferrer-Gallardo, V. J., Paz-Alonso, P. M., Caballero-Gaudes, C. & Rodríguez-Oroz, M. C. Interactions between functional networks in Parkinson’s disease mild cognitive impairment. Sci. Reports 2023 131 13 , 1–12 (2023). Vardy, Y., Bradshaw, J. L. & Iansek, R. Dual Target Identification and the Attentional Blink in Parkinson’s Disease. J. Clin. Exp. Neuropsychol. 25 , 361–375 (2003). Rafal, R. D., Posner, M. I., Walker, J. A. & Friedrich, F. J. Cognition and the basal ganglia separating mental and motor components of performance in parkinson’s disease. Brain 107 , 1083–1094 (1984). Cools, R. Dopaminergic modulation of cognitive function-implications for L-DOPA treatment in Parkinson’s disease. Neurosci. Biobehav. Rev. 30 , 1–23 (2006). Roy, M. A., Doiron, M., Talon-Croteau, J., Dupré, N. & Simard, M. Effects of Antiparkinson Medication on Cognition in Parkinson’s Disease: A Systematic Review. Can. J. Neurol. Sci. 45 , 375–404 (2018). Liu, C., Goel, P. & Kaeser, P. S. Spatial and temporal scales of dopamine transmission. Nat. Rev. Neurosci. 2021 226 22 , 345–358 (2021). Shen, W., Flajolet, M., Greengard, P. & Surmeier, D. J. Dichotomous dopaminergic control of striatal synaptic plasticity. Science (80-. ). 321 , 848–851 (2008). Dotov, D. G. et al. Biologically-variable rhythmic auditory cues are superior to isochronous cues in fostering natural gait variability in Parkinson’s disease. Gait Posture 51 , 64–69 (2017). Hove, M. J., Suzuki, K., Uchitomi, H., Orimo, S. & Miyake, Y. Interactive Rhythmic Auditory Stimulation Reinstates Natural 1/f Timing in Gait of Parkinson’s Patients. PLoS One 7 , e32600 (2012). Duppen, C. P. et al. Blending motor learning approaches for short-term adjustments to gait in people with Parkinson disease. Exp. Brain Res. 242 , 2853–2863 (2024). Bella, S. D., Benoit, C. E., Farrugia, N., Schwartze, M. & Kotz, S. A. Effects of musically cued gait training in Parkinson’s disease: Beyond a motor benefit. Ann. N. Y. Acad. Sci. 1337 , 77–85 (2015). Benoit, C. E. et al. Musically cued gait-training improves both perceptual and motor timing in Parkinson’s disease. Front. Hum. Neurosci. 8 , 1–11 (2014). Thaut, M. H. et al. Rhythmic auditory stimulation in gait training for Parkinson’s disease patients. Mov. Disord. 11 , 193–200 (1996). Mcintosh, G. C., Brown, S. H., Rice, R. R. & Thaut, M. H. patterns in patients with Parkinson ’ s disease. J. Neurol. Neurosurg. Psychiatry 22–26 (1997). Frank, M. J., Seeberger, L. C. & O’Reilly, R. C. By carrot or by stick: cognitive reinforcement learning in parkinsonism. Science (80-. ). 306 , 1940–3 (2004). Van Nuland, A. J. et al. Effects of dopamine on reinforcement learning in Parkinson’s disease depend on motor phenotype. Brain 143 , 3422–3434 (2021). Maquet, P. The role of sleep in learning and memory. Science (80-. ). 294 , 1048–1052 (2001). Girardeau, G. & Lopes-Dos-Santos, V. Brain neural patterns and the memory function of sleep. Science (80-. ). 374 , 560–564 (2021). Kleiner, M. et al. What ’ s new in Psychtoolbox-3 ? (2007). Additional Declarations There is NO Competing Interest. Supplementary Files supplementarymaterials.docx Supplementary Materials for Dopamine modulation of motor and implicit learning contributions to auditory temporal attention Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7301023","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":502165890,"identity":"e83f2603-7651-43b1-be8f-3a53cc8047bc","order_by":0,"name":"Arnaud Zalta","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA60lEQVRIiWNgGAWjYNACNiBmB+IPIDY70VqYmRkYZ4DYzKRoYeYBcQhp4Z999uBnnjIGe/5m/oOfbX5tk+cD2vbhYw5uLRLn8pKlec4xMEscZmaWzu27bdgGtE1y5jY81pzhMZDmbQM67TAzg3Ruz21GoBY2Zl48WuTP8Bj/BmrhkQfa8tuy57Y9QS0GZ3jMQLZIGBxmZpNm+HE7kaAWQ6AWyznnJAwMDzObWfY23E5uY2ZsxusXOaDDbrwps7GXO974+MaPP7dt57c3H/zwEZ/3IUACQjG2gckGguqRwB9SFI+CUTAKRsFIAQAkX0LmCssF4wAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-4918-6630","institution":"Aix Marseille Université","correspondingAuthor":true,"prefix":"","firstName":"Arnaud","middleName":"","lastName":"Zalta","suffix":""},{"id":502165891,"identity":"00e0ac02-bdb5-4b4b-be66-43bc8b57eb4e","order_by":1,"name":"Lena-Franziska Spitz","email":"","orcid":"","institution":"Heinrich-Heine University Düsseldorf","correspondingAuthor":false,"prefix":"","firstName":"Lena-Franziska","middleName":"","lastName":"Spitz","suffix":""},{"id":502165892,"identity":"dd7ad588-d65c-42d3-9744-7577391c061c","order_by":2,"name":"Prof Alfons Schnitzler","email":"","orcid":"","institution":"Duesseldorf University","correspondingAuthor":false,"prefix":"","firstName":"Prof","middleName":"Alfons","lastName":"Schnitzler","suffix":""},{"id":502165893,"identity":"cbfe32ba-0e19-4645-95d1-7f8b72c416c9","order_by":3,"name":"Benjamin Morillon","email":"","orcid":"https://orcid.org/0000-0002-0049-064X","institution":"Aix Marseille Université","correspondingAuthor":false,"prefix":"","firstName":"Benjamin","middleName":"","lastName":"Morillon","suffix":""},{"id":502165894,"identity":"93d3d59c-1f98-4625-b583-d716cffd3cf8","order_by":4,"name":"Esther Florin","email":"","orcid":"","institution":"Heinrich-Heine University Düsseldorf","correspondingAuthor":false,"prefix":"","firstName":"Esther","middleName":"","lastName":"Florin","suffix":""}],"badges":[],"createdAt":"2025-08-05 13:21:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7301023/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7301023/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90298174,"identity":"f4200d85-4b33-4f93-9c6d-1d596daf52d1","added_by":"auto","created_at":"2025-09-01 08:43:09","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":58532,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eExperimental design.\u003c/strong\u003e \u003cstrong\u003ea\u003c/strong\u003e Sequences of pure tones were presented binaurally on each trial. Three reference tones defining the beat frequency (or tempo; vertical lines) of the sequence preceded a mixture of on-beat and off-beat tones. Participants performed a beat discrimination task at the end of each trial by deciding whether the last tone of the sequence, a spectral deviant (785 Hz vs. 660 Hz), was on or off beat. Four tempi were investigated, at 0.6, 1.5, 2.2, and 3.5 Hz.\u003cstrong\u003eb\u003c/strong\u003e Individual difficulty level for healthy controls (black) and PD patients (grey) to reach threshold (75%) performance for a 2 Hz tempo. Difficulty was modulated by adjusting the density of distractors in the sequence (number of distractors per beat).\u003cstrong\u003e c.\u003c/strong\u003e Individual estimates of the optimal tempo of auditory temporal attention in the passive (blue and pale blue) and tracking (red and pink) conditions for healthy participants and PD patients. In the passive condition, participants performed the task without moving before the end of the sequence. In the tracking condition, participants performed the task while expressing the tempo by moving their index finger. ns: non-significant.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7301023/v1/012afe6f6ebcadd89d73e46a.png"},{"id":90298172,"identity":"33fb46f5-5a8f-44bc-bd54-b46ad701c974","added_by":"auto","created_at":"2025-09-01 08:43:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":80856,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDopamine modulation of motor contributions to auditory temporal attention.\u003c/strong\u003e \u003cstrong\u003ea.\u003c/strong\u003e Impact of tracking on performance for healthy controls (dark grey) and PD patients ON (cyan) or OFF (pink) DOPA medication. Difference in performance between the tracking and the passive conditions. \u003cstrong\u003eb-d.\u003c/strong\u003e Average performance for healthy participants \u003cstrong\u003e(b)\u003c/strong\u003e and PD patients ON \u003cstrong\u003e(c)\u003c/strong\u003e and OFF \u003cstrong\u003e(d)\u003c/strong\u003e DOPA per tempo in the passive (blue and pale blue) and tracking (red and rose) conditions.\u003cstrong\u003e \u003c/strong\u003eData were approximated with a polynomial function (plain line), and an optimal tempo (leading to a maximal performance) could be estimated (vertical line). The orange dot indicates the 2 Hz tempo used during the staircase titration procedure. *p \u0026lt; 0.05; ns: non-significant.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7301023/v1/9a23774fd3ae30f08b85cc08.png"},{"id":90298186,"identity":"294567fe-40d3-4c9f-879f-e1f0749642d6","added_by":"auto","created_at":"2025-09-01 08:43:09","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":50977,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDopaminergic modulation of audio-motor synchronization.\u003c/strong\u003e \u003cstrong\u003ea.\u003c/strong\u003e Tapping divergence for healthy controls (dark grey) and PD patients ON (cyan) or OFF (pink) DOPA medication compared to the theoretical frequency. \u003cstrong\u003eb-d.\u003c/strong\u003e Comparison between the tapping frequency for healthy participants \u003cstrong\u003e(b)\u003c/strong\u003e and PD patients ON \u003cstrong\u003e(d)\u003c/strong\u003e and OFF \u003cstrong\u003e(f)\u003c/strong\u003e DOPA with the tempo of the current trial. The dashed line represents a perfect correspondence between the two rhythms. *p \u0026lt; 0.05; ns: non-significant.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7301023/v1/8d4ebd8be76558d190114684.png"},{"id":90298183,"identity":"9fd9187a-0f19-4d03-bcf0-75f7eb976250","added_by":"auto","created_at":"2025-09-01 08:43:09","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":15326,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDopamine modulation of learning contributions to auditory temporal attention.\u003c/strong\u003e Learning effect: impact of participation order (ON- or OFF-DOPA medication) on performance evolution in PD patients. Difference of performance between the second and the first participation (p2-p1) for the PD patients. Patients performed the first participation ON- (left) or OFF-DOPA (right) medication (and vice-versa for the second).\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7301023/v1/71d10bb5ceaaa2fdb5f746a8.png"},{"id":92899340,"identity":"731e84fb-9f18-47ba-a176-b58bea37c839","added_by":"auto","created_at":"2025-10-06 20:48:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1509468,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7301023/v1/a2160ac7-a8a4-4a6a-a526-de636c50aa55.pdf"},{"id":90298170,"identity":"71b5f95d-7143-4d33-ad8e-e3a635009192","added_by":"auto","created_at":"2025-09-01 08:43:08","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":62049,"visible":true,"origin":"","legend":"\u003cp\u003eSupplementary Materials for Dopamine modulation of motor and implicit learning contributions to auditory temporal attention\u003c/p\u003e","description":"","filename":"supplementarymaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-7301023/v1/f5d7bc4447049aa142e0d233.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Dopamine modulation of motor and implicit learning contributions to auditory temporal attention","fulltext":[{"header":"Introduction","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eTo pay attention in time is essential for capturing relevant information and adapting behaviour to the external world. Temporal attention plays a key role in predicting and adjusting to dynamic external stimuli. However, unlike the continuous flow of sensory input, temporal attention \u0026mdash;even though flexible\u0026mdash; is constrained and rhythmic, a feature observed both behaviourally and neurophysiologically \u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eAuditory temporal attention and motor processes share similar temporal constraints, with optimal processing observed at ~\u0026thinsp;1.5-2 Hz \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Engaging in a motor act during an auditory temporal attention task further enhances performance \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Notably, even in the absence of overt movement, tasks involving temporal prediction or time perception recruit motor cortical areas \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. However, the precise neural correlates of this audio-motor interaction remain unclear, and whether these shared temporal constraints arise from a common neural substrate has yet to be determined.\u003c/p\u003e\u003cp\u003eDopamine plays a central role in action, motivation, and cognitive functions such as learning and prediction \u003csup\u003e\u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. The substantia nigra pars compacta, a key dopaminergic structure, contributes to motor control and regulates fine motor skills\u003csup\u003e\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. Dopamine is also essential for temporal processing, with the nigrostriatal pathway \u0026mdash;including the basal ganglia and striatum\u0026mdash; supporting both motor and timing functions\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Disrupting the midbrain dopaminergic network impairs time estimation \u003csup\u003e\u003cspan additionalcitationids=\"CR27 CR28 CR29\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e, and dopaminergic antagonists reduce timing accuracy \u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn Parkinson\u0026rsquo;s disease (PD), characterized by the degeneration of dopaminergic neurons, the core symptoms are motor-related, including akinesia, tremor, and bradykinesia \u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. Fine motor skills are also impaired in this pathology independently of this classical symptomatology \u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e. However, beyond these motor deficits, cognitive symptoms such as disruptions in decision-making, goal-directed behaviour \u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e and time perception \u003csup\u003e\u003cspan additionalcitationids=\"CR39 CR40 CR41 CR42\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e are reported. Mild cognitive impairment in Parkinson\u0026rsquo;s patients is well documented and affects a broad range of functions, including learning and attention\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan additionalcitationids=\"CR45 CR46 CR47\" citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e. Although both motor and cognitive symptoms are prominent in Parkinson\u0026rsquo;s disease, their relationship remains complex and not fully understood. Some studies report correlations between the severity of motor symptoms and the extent of cognitive decline and even identify potential neurophysiological markers of this association. Nevertheless, it remains unclear whether motor deficits directly contribute to cognitive deterioration\u003csup\u003e\u003cspan additionalcitationids=\"CR50 CR51\" citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eTo examine how periodic auditory temporal attention interacts with motor function and dopaminergic modulation, we tested PD patients both ON and OFF dopaminergic medication L-DOPA, alongside age-matched healthy controls. Participants performed an auditory temporal attention task under two conditions: passive listening and active motor tracking\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. In the passive condition, all groups exhibited comparable performance accuracy and shared the same optimal sampling rate, suggesting that internal temporal attention constraints remain preserved despite dopamine depletion. In contrast, motor tracking enhanced performance in healthy controls and PD patients when ON-DOPA, but not when OFF-DOPA, indicating that dopamine is necessary for motor-related performance gains. Finally, administering L-DOPA during a first session led to improved performance in a subsequent OFF-medication session, whereas starting OFF-medication did not produce such gains. These findings indicate that dopamine is not only essential for motor facilitation during auditory temporal attention but also plays a critical role in enabling learning across sessions.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Materials \u0026 methods","content":"\u003cp\u003e\u003cb\u003eParticipants.\u003c/b\u003e 26 parkinsonian patients (age mean: 66.5 years; age range: 54\u0026ndash;80 years; 24% of females) and 20 healthy age-matched participants (age mean: 64.8 years; age range: 52\u0026ndash;86 years; 20% of females) were recruited. Finally, nine Parkinsonian patients were excluded from the analysis because they did not complete the experiment. To view the details of the population, please refer to Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The experiment followed the local ethics guidelines from Heinrich Heine University, D\u0026uuml;sseldorf and was approved by the local ethics committee (study-no: 2019\u0026thinsp;\u0026minus;\u0026thinsp;488_1). Informed consent was obtained from all participants before the experiments. All healthy participants had normal audition and vision and reported no history of neurological or psychiatric disorders. We did not select participants based on musical training and a short survey made at the end of the experiment informed us that none of them were professional musicians.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eDemographic and clinical characteristics of the PD patients.\u003c/b\u003e m: male, f: female; BDI: Beck Depression Inventory; MDRS: Mattis Dementia Rating Scale; MDS-UPDRS 3: Unified Parkinson\u0026rsquo;s Disease Rating Scale; ON: under dopaminergic (L-dopa) medication; OFF: not under dopaminergic (L-dopa); Parkinson\u0026rsquo;s patients: Parkinson disease.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"11\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatient\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003egender\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBDI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eMDRS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDuration between initial diagnosis and experiment (years)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eMDS-UPDRS ON\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eMDS-UPDRS OFF\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eChallenge Dose of L-Dopa (mg)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eState condition 1/2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTYPE OF PD\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e80\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e140\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e200\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eON/OFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003etremor-dominant\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e65\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e137\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e250\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eON/OFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eequivalent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e67\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e139\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e150\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eON/OFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eequivalent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e4\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e60\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e141\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e300\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eON/OFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eequivalent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e5\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e77\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e141\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eOFF/ON\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e(akinetic-rigid)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e6\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e66\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e135\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e200\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eOFF/ON\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eakinetic-rigid\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e7\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e61\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e142\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e300\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eOFF/ON\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eequivalent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e8\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e62\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e138\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e200\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eOFF/ON\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eequivalent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e9\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e69\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e135\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e300\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eON/OFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eequivalent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e10\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003ef\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e56\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e142\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e150\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eON/OFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eequivalent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e11\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e67\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e139\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eOFF/ON\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003etremor-dominant\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e12\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e72\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e139\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e200\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eOFF/ON\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eequivalent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e13\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e72\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e137\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e250\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eOFF/ON\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eakinetic-rigid\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e14\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e73\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e143\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e250\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eOFF/ON\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eequivalent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e15\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003ef\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e73\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e139\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e250\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eON/OFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eakinetic-rigid\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e16\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e54\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e142\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eOFF/ON\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eequivalent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e17\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003ef\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e59\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e137\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e150\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eON/OFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eequivalent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e18\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003ef\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e64\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e139\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e150\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eOFF/ON\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eequivalent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e19\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003ef\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e58\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e136\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eOFF/ON\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ehypokinetic-rigid\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e20\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003ef\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e69\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e131\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eON/OFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eequivalent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e21\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003ef\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e68\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e135\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e200\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eON/OFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ehypokinetic-rigid\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e22\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003ef\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e75\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e124\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e150\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eON/OFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ehypokinetic-rigid\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e23\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e70\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e137\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eON/OFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ehypokinetic-rigid\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e24\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e59\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e140\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e200\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eON/OFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003etremor-dominant\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e25\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e57\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e132\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e200\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eON/OFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003etremor-dominant\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e26\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003em\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e63\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e137\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eON/OFF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ehypokinetic-rigid\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAverage\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e66,00\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11,3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e137,6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e8,7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e22,4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e35,8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e180,8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eExperimental design.\u003c/b\u003e The experiment was adapted from \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Auditory stimuli were sampled at 44 100 Hz and presented binaurally at a comfortable hearing level via headphones in a quiet room, using the Psychophysics-3 toolbox \u003csup\u003e\u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e78\u003c/span\u003e\u003c/sup\u003e and additional custom scripts written for MATLAB (The Mathworks). The instructions were displayed visually on a mid-grey background of a laptop screen situated at a viewing distance of 50 cm. The screen had a spatial resolution of 1920 by 1080 pixels and a vertical refresh rate of 60 Hz. On each trial, participants had to fixate a cross, located at the centre of the screen, to get a constant visual stimulation. Each trial consisted of a sequence of pure tones, qualified as reference, targets, and distractors (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). Three reference tones defining the beat of the sequence preceded a mixture of on-beat (target) and off-beat (distractor) tones. Participants performed a beat discrimination task at the end of each trial, by deciding whether the last tone of the sequence, a spectral deviant (785 Hz vs. 660 Hz), was on or off beat. While on-beat stimuli were providing the beat, crucially, off-beat stimuli had a distracting influence. This interleaved delivery of sensory events forced participants to track the beat throughout the entire duration of the sequence while minimising the interference of aperiodic events. This protocol thus ensured that their attentional focus was temporally modulated over an extended time period.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThis design implies that the last inter-stimulus interval (ISI) did not always correspond to the beat period of the trial. Distractors could occur between the last target tone and the deviant. Tone frequencies were selected to avoid potential bone transmission (660/785 Hz). 4 beat frequencies (or tempi) of 0.6, 1.5, 2.2, and 3.5 Hz were presented to the participant to span the entire range of discernible beats \u003csup\u003e\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e,\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e. We orthogonalized tempi and tone duration by fixing tone duration to 22.5 ms. Tones dampening length was 10% of their duration, and tone attenuation was 40 dB. Trials had pseudo-random durations (~\u0026thinsp;2\u0026ndash;12 s) but included in each tempo at least four targets (and up to 22; reference tones and deviant excluded) and lasted at least 2 s. These constraints were chosen to enable the deployment of temporal attention in all tempi. The density of distractors per sequence (i.e., the number of distractors per beat) was titrated individually (see below). Distractors appeared randomly between targets, with the constraint that all ISI within the sequence should be of at least 9% of the beat period (e.g., ISI\u0026thinsp;\u0026gt;\u0026thinsp;90 ms for a 1 Hz beat). This ensured that tones did not appear concomitantly. The deviant target was occurring either on or off beat (50/50%). When the deviant was off beat, it appeared randomly within a window corresponding to one beat period and centred around the expected beat.\u003c/p\u003e\u003cp\u003eParticipants performed \u0026lsquo;passive\u0026rsquo; blocks, in which they executed the task while staying completely still during the duration of the trial, not moving any part of their body. Additionally, participants performed \u0026lsquo;tracking\u0026rsquo; blocks, in which they were required to follow the beat by moving their (left or right, at their convenience) index finger, on a noiseless pad or on a key of the experiment\u0026rsquo;s laptop keyboard, from the beginning of the sequence (the 2nd reference tone). In essence, the tracking condition is a variation of the synchronisation-continuation paradigm \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. For PD patients, two passive and tracking conditions were performed, one with (ON) and one without (OFF) L-DOPA medication. For the OFF-L-DOPA state, patients were recorded in the clinically defined medication OFF state following withdrawal of dopaminergic medication overnight for at least 12 hours prior to study completion. For the ON L-DOPA state, patients were measured in their best clinical ON state. The ON- and OFF-DOPA states occurred on different days, if the ON measurement was performed first. Otherwise, the ON measurement was made after the OFF-state measurement and at least 30 minutes after the intake of up to 1.5 times their morning L-DOPA dosage in the form of a fast-acting dopamine.\u003c/p\u003e\u003cp\u003eEach participant started the experiment with a short training block. The beat frequency was fixed to 2 Hz, and the density of distractors was at first equal to zero and increased progressively up to 0.4 distractors per beat. Participants were instructed not to move during the trials (as in the passive condition). Then, participants listened to the 4 tempi at least 1 time each. Following this short training block, participants performed a psychophysical staircase where the density of distractors was the varying parameter. The staircase was set to obtain\u0026thinsp;~\u0026thinsp;75% of categorisation performance. Participants performed 40 trials per tempo per condition. Tempi were pseudo-randomly alternating in blocks of 20 trials, each with or without tracking demand. Feedback was provided after each trial to indicate correct/incorrect responses, and more general performance feedback, indicating the total number of correct responses was given after every block, for motivational purposes. Trials with outlier reaction times (more than two standard deviations away from the mean per participant, condition, and tempo) were excluded.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTiming of motor acts in the tracking condition.\u003c/b\u003e To investigate the ability of participants to actively follow the beat, we extracted the timing of individual motor acts in the tracking condition. For each trial, we computed the standard deviation of the inter-tap intervals.\u003c/p\u003e\u003cp\u003e\u003cb\u003eEstimation of an optimal beat frequency.\u003c/b\u003e To estimate the tempo at which performance would be maximal (/minimal), variations of performance across tempi were approximated at the individual level with a third-order polynomial function f(x)\u0026thinsp;=\u0026thinsp;ax\u003csup\u003e3\u003c/sup\u003e\u0026thinsp;+\u0026thinsp;bx\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;+\u0026thinsp;cx\u0026thinsp;+\u0026thinsp;d, and the coordinates of the local maxima α (/minima β) were extracted according to the functions:\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:{\\alpha\\:}=\\frac{-b-\\sqrt{{\\delta\\:}}}{3a};{\\beta\\:}=\\frac{-b+\\sqrt{{\\delta\\:}}}{3a}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ewhere \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\delta\\:={b}^{2}-3ac\\)\u003c/span\u003e\u003c/span\u003e with δ\u0026thinsp;\u0026gt;\u0026thinsp;0. We used a third-order polynomial function, as it is the best (i.e. most flexible) model that allows estimating one maximum without ambiguity (higher order models accept multiple maxima). A second-order function was used for visualisation purposes when fitting the group-level performance profile.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStatistical procedures\u003c/b\u003e. All analyses were performed at the single-subject level and followed by standard non-parametric two-sided tests at the group level (Wilcoxon paired signed-rank, unpaired Mann-Whitney or Friedman tests). The divergence in participants' tapping from the tempo of the presented sequences was calculated using the norm of the difference between their tapping frequency and the beat frequency.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eParkinson\u0026rsquo;s disease does not affect auditory temporal attention capacities.\u003c/b\u003e Sequences of pure tones were presented on each trial, from 2 to ~\u0026thinsp;20 s. Three reference stimuli defining the tempo (or beat frequency) of the isochronous event sequence preceded a mixture of on-beat and off-beat stimuli. Participants performed a beat discrimination task at the end of each trial, by deciding whether the last stimulus of the sequence, a deviant, was on or off beat (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). While on-beat stimuli were reinforcing the beat, crucially, off-beat stimuli had a distracting influence. This interleaved delivery of sensory events forced participants to track the beat throughout the entire duration of the sequence while minimising the interference of aperiodic distractors. This protocol ensures that participant\u0026rsquo;s attentional focus is temporally modulated over an extended time period. The density of distractors (i.e., number of distractors per beat) was titrated for each participant prior to the experiment to reach threshold performance for a 2 Hz tempo (see Methods). Four tempi were then investigated, with isochronous tempi of 0.6, 1.5, 2.2, and 3.5 Hz, to span most of the range of discernible tempi \u003csup\u003e\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e,\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eParticipants completed two conditions in this task. A passive condition, in which they performed the task while staying completely still throughout each trial. Participants performed also a tracking condition, in which they tapped the beat in phase, with their index finger (see methods). Therefore, the absence or presence of overt movement was the single difference between the two conditions. While it is not possible to control for the covert involvement of motor and/or premotor structures during temporal attention tasks, comparing passive and tracking conditions allows us to quantify the influence of overt (relative to covert) motor activity on the precision of temporal attention.\u003c/p\u003e\u003cp\u003eTo investigate whether dopamine dysfunction impacts auditory periodic temporal attention, PD patients and age-matched healthy participants performed the same experiment. The average difficulty level (density of distractors) estimated during a staircase titration procedure was around 0.6 for the two groups (controls: M\u0026thinsp;=\u0026thinsp;0.69, SD\u0026thinsp;=\u0026thinsp;0.63; Parkinson\u0026rsquo;s patients: M\u0026thinsp;=\u0026thinsp;0.49, SD\u0026thinsp;=\u0026thinsp;0.22; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb) and did not significantly differ across groups (unpaired Mann-Whitney test: U\u0026thinsp;=\u0026thinsp;159, p\u0026thinsp;=\u0026thinsp;0.73, r\u0026thinsp;=\u0026thinsp;0.06, Bayes Factor (BF)\u0026thinsp;=\u0026thinsp;0.57). Moreover, during the main experiment, the two groups did not differ significantly in performance accuracy (% correct responses) across tempi and conditions (mean controls\u0026thinsp;=\u0026thinsp;0.70; mean Parkinson\u0026rsquo;s patients\u0026thinsp;=\u0026thinsp;0.69; Friedman test, main effect of performance: U\u0026thinsp;=\u0026thinsp;161, p\u0026thinsp;=\u0026thinsp;0.80, r\u0026thinsp;=\u0026thinsp;0.04, BF\u0026thinsp;=\u0026thinsp;0.33).\u003c/p\u003e\u003cp\u003e\u003cb\u003eAge and dopamine modulation do not affect the optimal rate of auditory temporal attention.\u003c/b\u003e We then investigated whether dopamine modulation affects the optimal rate of auditory temporal attention in this task. First, performance varied significantly with tempo across all conditions (listening and tracking), participant groups (controls and PD patients), and sessions (ON and OFF DOPA; Friedman tests: all χ2(3)\u0026thinsp;\u0026gt;\u0026thinsp;19, all p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). This notably generalizes our previous result in an elderly population, that auditory periodic temporal attention is rate-restricted\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThen, for each condition (passive and tracking) and group (healthy controls and PD patients), the optimal rate was estimated by fitting participants\u0026rsquo; accuracy across tempi (see Methods). The optimal beat frequency estimated with individual fits was around 1.5 Hz in both conditions and groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec) and did not differ significantly across conditions (passive vs. tracking: controls: Wilcoxon test: Z\u0026thinsp;=\u0026thinsp;0.45, p\u0026thinsp;=\u0026thinsp;0.65, BF\u0026thinsp;=\u0026thinsp;0.43; parkinsonian patients: Z\u0026thinsp;=\u0026thinsp;0.69, p\u0026thinsp;=\u0026thinsp;0.49, BF\u0026thinsp;=\u0026thinsp;0.39) nor across groups (Mann-Whitney test: U\u0026thinsp;=\u0026thinsp;140, p\u0026thinsp;=\u0026thinsp;0.37, r\u0026thinsp;=\u0026thinsp;0.15, BF\u0026thinsp;=\u0026thinsp;0.49). Overall, these results confirm previous findings that periodic auditory temporal attention is rate-restricted and optimal around 1.5 Hz\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eTo investigate whether L-DOPA medication has an impact on the auditory temporal attention capacities of PD patients, we made the distinction between sessions where patients were ON- or OFF-DOPA medication. We first observed that the optimal beat frequency estimated with individual fits was around 1.5 Hz in all (ON- or OFF-DOPA and listen or tracking condition) sessions and did not differ significantly across them (Friedman test: χ2(3)\u0026thinsp;=\u0026thinsp;0.48, p\u0026thinsp;=\u0026thinsp;0.9; supplementary Fig.\u0026nbsp;1a).\u003c/p\u003e\u003cp\u003e\u003cb\u003eDopamine modulation of motor contribution to auditory temporal attention.\u003c/b\u003e We then investigated whether motor activity helps synchronise temporal fluctuations of attention with the timing of events in a task-relevant stream by comparing the passive and tracking conditions in both healthy controls and PD patients. We observed a significant increase in performance accuracy during motor-tracking compared to passive listening conditions, across groups of participants and tempi (Wilcoxon paired signed-rank test: Z\u0026thinsp;=\u0026thinsp;3.63, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). For PD patients, when ON-DOPA, we observed such a significant increase in performance accuracy (Wilcoxon test: Z\u0026thinsp;=\u0026thinsp;2.53, p\u0026thinsp;=\u0026thinsp;0.011; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea \u0026amp; supplementary Fig.\u0026nbsp;1b), but this was not the case when the same patients performed the same experiment OFF-DOPA (Wilcoxon test: Z\u0026thinsp;=\u0026thinsp;0.26, p\u0026thinsp;=\u0026thinsp;0.80, BF\u0026thinsp;=\u0026thinsp;0.33; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea \u0026amp; supplementary Fig.\u0026nbsp;1c). The difference in motor benefit across ON- and OFF-DOPA state was significant (Wilcoxon test: Z\u0026thinsp;=\u0026thinsp;2.20, p\u0026thinsp;=\u0026thinsp;0.028; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eMore precisely, post-hoc tests indicated that overt motor tracking significantly increased performance when healthy control participants performed the task between 0.6 and 2.2 Hz (Wilcoxon tests: 0.6 Hz: Z\u0026thinsp;=\u0026thinsp;3.00, p\u0026thinsp;=\u0026thinsp;0.003; 1.5 Hz: Z\u0026thinsp;=\u0026thinsp;2.41, p\u0026thinsp;=\u0026thinsp;0.016; 2.2 Hz: Z\u0026thinsp;=\u0026thinsp;3.79, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; 3.5 Hz: Z\u0026thinsp;=\u0026thinsp;0.15, p\u0026thinsp;=\u0026thinsp;0.88, BF\u0026thinsp;=\u0026thinsp;0.24; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). The motor benefit was maximal at 2.2 Hz, replicating previous findings\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. For PD patients in the ON-DOPA state, this motor benefit was also maximal and significant at 2.2 Hz (Wilcoxon test: Z\u0026thinsp;=\u0026thinsp;3.30, p\u0026thinsp;=\u0026thinsp;0.001; other tempi: all Z\u0026thinsp;\u0026lt;\u0026thinsp;1.73, all p\u0026thinsp;\u0026gt;\u0026thinsp;0.08 all BF\u0026thinsp;\u0026lt;\u0026thinsp;0.56; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec).\u003c/p\u003e\u003cp\u003eWe finally tested whether the motor benefit observed in PD patients in the ON-DOPA state correlated with their L-DOPA challenge dosage and MDS-Unified Parkinson's Disease Rating Scale (UPDRS) part 3 scores were assessed during the experimental session. To note, the MDS-UPDRS part 3 score measures the severity of PD by rating motor symptoms across multiple domains. Higher scores indicate more severe impairment\u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e\u003c/sup\u003e. There was a significant negative correlation between motor benefit and L-DOPA dosage (Pearson correlation, \u003cem\u003er\u003c/em\u003e (15)\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.50, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04), indicating that higher doses were associated with reduced motor benefit. In contrast, no significant correlation was found between motor benefit and MDS-UPDRS scores (Pearson correlation, \u003cem\u003er\u003c/em\u003e (15)\u0026thinsp;=\u0026thinsp;0.12, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.66).\u003c/p\u003e\u003cp\u003e\u003cb\u003eDopamine contribution to motor adaptation.\u003c/b\u003e We next investigated participants\u0026rsquo; ability to adapt their motor acts to the tempo of the auditory stream by comparing the tempo of their tapping movements to that of the concurrently presented rhythm. We computed the tapping divergence\u0026mdash;the deviation between the presented and reproduced tempi (see Methods)\u0026mdash;and compared it between groups and sessions. Patients in the ON-DOPA state were able to match the presented tempi similarly to healthy controls (Wilcoxon signed-rank test: z\u0026thinsp;=\u0026thinsp;0.46, p\u0026thinsp;=\u0026thinsp;0.64, BF\u0026thinsp;=\u0026thinsp;0.34; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea, b \u0026amp;c). In contrast, in the OFF-DOPA state, patients showed a clear difficulty in adapting their movements to the tempo of the external auditory stimulus. We found a significant divergence from the tapping frequency of both healthy controls (Wilcoxon signed-rank test: z\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;3.59, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed) and the same patients in the ON-DOPA state (One sample t test: t = -5.88, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Patients in the OFF-DOPA state tapped essentially at a frequency of around 1.5 Hz, independently of the stimulus tempo. In other words, at tempos above and below 1.5 Hz, they were unable to adapt their tapping speed to the stimulus.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eDopamine contribution to implicit learning.\u003c/b\u003e Finally, we examined whether the order in which PD patients performed the task \u0026mdash;first ON-DOPA then OFF-DOPA, or the reverse\u0026mdash; had any effect on the results. Our rationale was that learning effects often occur across repeated sessions of the same task, and L-DOPA intake during the first participation could positively modulate this effect. Parkinson\u0026rsquo;s patients were therefore divided into two groups: those who began in the ON-DOPA state (n\u0026thinsp;=\u0026thinsp;8; and performed the second session OFF-DOPA) and those who started in the OFF-DOPA state (n\u0026thinsp;=\u0026thinsp;9; and performed the second session ON-DOPA). We calculated the change in overall performance (across tempi) between the first and second session to assess learning and the potential influence of medication.\u003c/p\u003e\u003cp\u003eWe observed a significant learning effect in both passive and tracking conditions for patients who began ON-DOPA (Wilcoxon tests: passive: Z\u0026thinsp;=\u0026thinsp;2.52, p\u0026thinsp;=\u0026thinsp;0.012; tracking: Z\u0026thinsp;=\u0026thinsp;2.38, p\u0026thinsp;=\u0026thinsp;0.017). In contrast, we didn\u0026rsquo;t find any learning effect in patients who started OFF-DOPA (passive: Z\u0026thinsp;=\u0026thinsp;0.06, p\u0026thinsp;=\u0026thinsp;0.95, BF\u0026thinsp;=\u0026thinsp;0.23; tracking: Z\u0026thinsp;=\u0026thinsp;1.48, p\u0026thinsp;=\u0026thinsp;0.14, BF\u0026thinsp;=\u0026thinsp;0.89). This learning effect was similar between the passive and tracking conditions (Wilcoxon tests, passive vs. tracking conditions: ON-DOPA first: Z\u0026thinsp;=\u0026thinsp;1.68, p\u0026thinsp;=\u0026thinsp;0.09, BF\u0026thinsp;=\u0026thinsp;0.40; OFF-DOPA first: Z\u0026thinsp;=\u0026thinsp;1.36, p\u0026thinsp;=\u0026thinsp;0.17, BF\u0026thinsp;=\u0026thinsp;0.63) and significantly different in the ON-DOPA-first group compared to the OFF-DOPA-first group (Wilcoxon rank sum test: W\u0026thinsp;=\u0026thinsp;100, p\u0026thinsp;=\u0026thinsp;0.006 ; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). These results suggest that learning across sessions in this task is modulated by L-DOPA intake in PD patients.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eHow does dopamine affect the audio-motor synergy in periodic temporal attention? Here we extend our understanding of the behavioural and neurophysiological bases of audio-motor interaction by demonstrating that: (1) dopamine does not modulate the intrinsic rhythm of auditory temporal attention (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec); (2) L-DOPA restores the synergy between auditory temporal attention and motor acts in patients with Parkinson\u0026rsquo;s disease (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e); (3) Dopamine affects fine motor performance: PD patients in the ON-DOPA state synchronize their motor acts with auditory stimuli like healthy controls, unlike in the OFF-DOPA state (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e); (4) Dopamine promotes implicit learning: only PD patients ON-DOPA state during the first session showed a learning effect across sessions in our task (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThese results extend previous studies on the relationship between dopamine, motor acts, time estimation, and attention \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u003c/sup\u003e, by showing that cortical areas classically associated with motor control are also engaged in timing and temporal prediction functions \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e,\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e\u003c/sup\u003e. Some models specifically linked the basal ganglia and dopaminergic pathways with the motor cortical area as part of the time estimation mechanism \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Using PD patients as a model of dopamine depletion, we found that the perceptual benefit of overt motor activity disappears when dopamine is lacking during our temporal attentional task. In contrast, in healthy controls or PD patients in the ON-DOPA state, overtly tracking the beat during the experiment enhances performance \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Dopamine, thus, could be crucial for the interactions between motor processes and high cognitive functions such as auditory temporal attention. Coupled oscillator models have been used to describe how synchronization between these systems can emerge, suggesting that motor-attention synergy may underlie the observed effects \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Supporting this, coherence analysis in PD patients show that dopamine enhances cortical and muscular connectivity during bilateral gait control \u003csup\u003e\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e\u003c/sup\u003e. Reduced connectivity between attention and sensorimotor networks has also been associated with mild cognitive impairment in PD patients \u003csup\u003e\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e\u003c/sup\u003e. However, further investigation is needed to address this question, as our study cannot disentangle the motor disruption effect from the potential role of dopamine in audio-motor connectivity.\u003c/p\u003e\u003cp\u003eWe didn\u0026rsquo;t find a difference in task difficulty between PD patients and healthy controls. This may reflect preserved attentional capacities in PD patients, particularly when symptoms are chronically managed with L-DOPA, as suggested by some studies, despite reports of broader cognitive impairments \u003csup\u003e\u003cspan additionalcitationids=\"CR62 CR63\" citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e\u003c/sup\u003e. One possible explanation for the overall lack of difference in attentional performance between ON and OFF L-DOPA states is that chronic L-DOPA treatment may balance the synaptic degradation typically seen in Parkinson\u0026rsquo;s disease \u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. Dopamine has been shown to support synaptic maintenance and regeneration, helping to preserve connectivity \u003csup\u003e\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e,\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eMoreover, our results show that dopamine does not affect the intrinsic frequency of temporal attention but specifically enables motor-driven performance gains. Dopamine could be a key modulator not only of the motor processes but also of the connectivity between motor and cognitive processes. Interestingly, the reported ability to use the auditory rhythm in combination with the motor act to improve perception aligns with studies reporting gait improvement with auditory stimulation, suggesting its perceptual and motor benefit in a Parkinson\u0026rsquo;s population \u003csup\u003e\u003cspan additionalcitationids=\"CR68 CR69 CR70 CR71 CR72\" citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e\u003c/sup\u003e. This mechanism likely fails in PD patients due to motor symptoms \u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e that impair their ability to move in phase with attentional dynamics. This interpretation is supported by the increased tapping divergence observed in PD patients in the OFF-DOPA state. A similar absence of modulation has been reported when motor tracking is deliberately decoupled from attention \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Biologically, the motor recovery observed with L-DOPA may result from an acute effect driven by increased dopamine levels. But further studies are needed to disentangle the chronic effects from the acute motor benefits of L-DOPA.\u003c/p\u003e\u003cp\u003eOf note, we found no correlation between clinical scores, such as the MDS-UPDRS part 3, and the tracking benefit observed in the task. Instead, the behavioural metric correlated negatively only with L-DOPA challenge dosage, which is expected since medication levels typically increase with symptom severity. The absence of a link between clinical and behavioural measures suggests that our task captures motor-cognitive interactions not reflected in standard clinical assessments. However, given our relatively small sample size, these correlations (or the absence of them) should be interpreted with caution. A larger sample is needed to robustly test clinical hypotheses. Nonetheless, our findings highlight the potential of this task to isolate specific motor-attention processes that warrant further investigation.\u003c/p\u003e\u003cp\u003eFinally, PD patients OFF-DOPA state during their first experimental participation showed no learning benefit in the second participation (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). In contrast, when PD patients performed the task first ON-DOPA state, a learning effect was observed, indicating that training could improve performance. These results also support the presence of implicit learning deficits in PD patients, a finding that has been debated in the literature \u003csup\u003e\u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e74\u003c/span\u003e,\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e\u003c/sup\u003e. A limitation of the study is that PD patients who first performed the task in the ON-DOPA state completed the second session the following day, while those who started in the OFF-DOPA state performed both sessions on the same day. Since sleep can also positively influence learning \u003csup\u003e\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e,\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e\u003c/sup\u003e, further investigation is needed to clarify whether the observed learning effect stems from dopaminergic modulation, sleep-related consolidation, or both \u0026mdash;especially given that our results are consistent with all these explanations.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn sum, our results indicate that the dopaminergic system is not essential for auditory periodic temporal attention itself but plays a key role in modulating the motor contribution to auditory attention and in learning within this task. Dopamine thus appears crucial for regulating motor and learning processes and their interaction with cognitive functions such as auditory perception and temporal attention.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability Statement.\u0026nbsp;\u003c/strong\u003eThe data reported in this paper, along with the analysis pipelines, can be accessed upon request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding and Disclosure.\u003c/strong\u003e AZ is supported by the Fondation pour la Recherche Médicale (FRM) (SPF202209015740).\u0026nbsp;B.M.\u0026nbsp;has received funding from the European Research Council\u0026nbsp;(ERC, SPEEDY, ERC-CoG-101043344). The authors have nothing to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement.\u003c/strong\u003e We thank all the patients and healthy participants for their participation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions.\u0026nbsp;\u003c/strong\u003eConceptualization: B.M., E.F. \u0026amp; A.Z. Data collection: E.F. \u0026amp; L.S. Methodology: B.M. \u0026amp; A.Z. Investigation: B.M. \u0026amp; A.Z. Visualization: A.Z. Funding acquisition: B.M, E.F. \u0026amp; A.S. Project administration: B.M., E.F. and A.Z. Supervision: B.M. and E.F. Writing—original draft: A.Z. Writing—review and editing: all the authors.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eZalta, A., Petkoski, S. \u0026amp; Morillon, B. Natural rhythms of periodic temporal attention. \u003cem\u003eNat. Commun.\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 1\u0026ndash;12 (2020).\u003c/li\u003e\n \u003cli\u003eHelfrich, R. F. \u003cem\u003eet al.\u003c/em\u003e Neural Mechanisms. \u003cem\u003eNeuron\u003c/em\u003e \u003cstrong\u003e99\u003c/strong\u003e, 854-865.e5 (2018).\u003c/li\u003e\n \u003cli\u003eFiebelkorn, I. C. \u0026amp; Kastner, S. A Rhythmic Theory of Attention. \u003cem\u003eTrends Cogn. Sci.\u003c/em\u003e \u003cstrong\u003e23\u003c/strong\u003e, 87\u0026ndash;101 (2019).\u003c/li\u003e\n \u003cli\u003eRe, D., Inbar, M., Richter, C. G. \u0026amp; Landau, A. N. Feature-Based Attention Samples Stimuli Report Feature-Based Attention Samples Stimuli Rhythmically. \u003cem\u003eCurr. Biol.\u003c/em\u003e 1\u0026ndash;7 (2019) doi:10.1016/j.cub.2019.01.010.\u003c/li\u003e\n \u003cli\u003eMacDougall, H. G. \u0026amp; Moore, T. S. Marching to the beat of the same drummer: the spontaneous tempo of human locomotion. \u003cem\u003eJ. Appl. Physiol.\u003c/em\u003e \u003cstrong\u003e99\u003c/strong\u003e, 1164\u0026ndash;1173 (2005).\u003c/li\u003e\n \u003cli\u003eRepp, B. H. \u0026amp; Su, Y. Sensorimotor synchronization : A review of recent research ( 2006 \u0026ndash; 2012 ). (2013) doi:10.3758/s13423-012-0371-2.\u003c/li\u003e\n \u003cli\u003eMorillon, B., Arnal, L. H., Schroeder, C. E. \u0026amp; Keitel, A. Prominence of delta oscillatory rhythms in the motor cortex and their relevance for auditory and speech perception. \u003cem\u003eNeurosci. Biobehav. Rev.\u003c/em\u003e \u003cstrong\u003e107\u003c/strong\u003e, 136\u0026ndash;142 (2019).\u003c/li\u003e\n \u003cli\u003eGupta, A., Matthews, T. E., Penhune, V. B. \u0026amp; Morillon, B. Behavioral Evidence for Two Modes of Attention. \u003cem\u003ebioRxiv\u003c/em\u003e 2024.09.12.612641 (2024) doi:10.1101/2024.09.12.612641.\u003c/li\u003e\n \u003cli\u003eMorillon, B. \u0026amp; Baillet, S. Motor origin of temporal predictions in auditory attention. \u003cem\u003eProc. Natl. Acad. Sci.\u003c/em\u003e \u003cstrong\u003e114\u003c/strong\u003e, E8913\u0026ndash;E8921 (2017).\u003c/li\u003e\n \u003cli\u003eMorillon, B., Schroeder, C. E. \u0026amp; Wyart, V. Motor contributions to the temporal precision of auditory attention. \u003cem\u003eNat. Commun.\u003c/em\u003e \u003cstrong\u003e5\u003c/strong\u003e, 1\u0026ndash;9 (2014).\u003c/li\u003e\n \u003cli\u003eTe Rietmolen, N., Strijkers, K. \u0026amp; Morillon, B. Moving rhythmically can facilitate naturalistic speech perception in a noisy environment. \u003cem\u003eProc. B\u003c/em\u003e \u003cstrong\u003e292\u003c/strong\u003e, (2025).\u003c/li\u003e\n \u003cli\u003eDe Kock, R., Gladhill, K. A., Ali, M. N., Joiner, W. M. \u0026amp; Wiener, M. How movements shape the perception of time. \u003cem\u003eTrends Cogn. Sci.\u003c/em\u003e \u003cstrong\u003e25\u003c/strong\u003e, 950\u0026ndash;963 (2021).\u003c/li\u003e\n \u003cli\u003eSchmidt-Kassow, M., Heinemann, L. V, Abel, C. \u0026amp; Kaiser, J. Auditory-motor synchronization facilitates attention allocation. \u003cem\u003eNeuroimage\u003c/em\u003e \u003cstrong\u003e82\u003c/strong\u003e, 101\u0026ndash;106 (2013).\u003c/li\u003e\n \u003cli\u003eCannon, J. J. \u0026amp; Patel, A. D. How Beat Perception Co-opts Motor Neurophysiology. \u003cem\u003eTrends Cogn. Sci.\u003c/em\u003e \u003cstrong\u003e25\u003c/strong\u003e, 137\u0026ndash;150 (2021).\u003c/li\u003e\n \u003cli\u003eCoull, J. T. Functional Anatomy of the Attentional Modulation of Time Estimation. \u003cem\u003eScience (80-. ).\u003c/em\u003e \u003cstrong\u003e303\u003c/strong\u003e, 1506\u0026ndash;1508 (2004).\u003c/li\u003e\n \u003cli\u003eZalta, A., Large, E. W., Sch\u0026ouml;n, D. \u0026amp; Morillon, B. Neural dynamics of predictive timing and motor engagement in music listening. \u003cem\u003eSci. Adv.\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e, 2525 (2024).\u003c/li\u003e\n \u003cli\u003eThiele, A. \u0026amp; Bellgrove, M. A. Neuromodulation of Attention. \u003cem\u003eNeuron\u003c/em\u003e \u003cstrong\u003e97\u003c/strong\u003e, 769\u0026ndash;785 (2018).\u003c/li\u003e\n \u003cli\u003eSchultz, W., Dayan, P. \u0026amp; Montague, P. R. A neural substrate of prediction and reward. \u003cem\u003eScience (80-. ).\u003c/em\u003e \u003cstrong\u003e275\u003c/strong\u003e, 1593\u0026ndash;1599 (1997).\u003c/li\u003e\n \u003cli\u003eSchultz, W. Dopamine reward prediction-error signalling: a two-component response. \u003cem\u003eNat. Rev. Neurosci. 2016 173\u003c/em\u003e \u003cstrong\u003e17\u003c/strong\u003e, 183\u0026ndash;195 (2016).\u003c/li\u003e\n \u003cli\u003eBerke, J. D. What does dopamine mean? \u003cem\u003eNat. Neurosci.\u003c/em\u003e \u003cstrong\u003e21\u003c/strong\u003e, 787\u0026ndash;793 (2018).\u003c/li\u003e\n \u003cli\u003eBova, A. \u003cem\u003eet al.\u003c/em\u003e Precisely-timed dopamine signals establish distinct kinematic representations of skilled movements. \u003cem\u003eElife\u003c/em\u003e \u003cstrong\u003e9\u003c/strong\u003e, 1\u0026ndash;141 (2020).\u003c/li\u003e\n \u003cli\u003eHunter, J., Bova, A., Stevens, A. \u0026amp; Leventhal, D. K. Dopamine neuron stimulation induces context-dependent abnormal involuntary movements in healthy rats. \u003cem\u003eISCIENCE\u003c/em\u003e \u003cstrong\u003e25\u003c/strong\u003e, 103974 (2022).\u003c/li\u003e\n \u003cli\u003ePhillips, C. D., Hodge, A. T., Myers, C. C., Leventhal, D. K. \u0026amp; Burgess, C. R. Striatal Dopamine Contributions to Skilled Motor Learning. (2024) doi:10.1523/JNEUROSCI.0240-24.2024.\u003c/li\u003e\n \u003cli\u003eJones, C. R. G., Malone, T. J. L., Dirnberger, G., Edwards, M. \u0026amp; Jahanshahi, M. Basal ganglia, dopamine and temporal processing: Performance on three timing tasks on and off medication in Parkinson\u0026rsquo;s disease. (2008) doi:10.1016/j.bandc.2008.02.121.\u003c/li\u003e\n \u003cli\u003eBuhusi, C. V. \u0026amp; Meck, W. H. What makes us tick? Functional and neural mechanisms of interval timing. \u003cem\u003eNat. Rev. Neurosci.\u003c/em\u003e \u003cstrong\u003e6\u003c/strong\u003e, 755\u0026ndash;765 (2005).\u003c/li\u003e\n \u003cli\u003eBreska, A. \u0026amp; Ivry, R. B. Double dissociation of single-interval and rhythmic temporal prediction in cerebellar degeneration and Parkinson\u0026rsquo;s disease. \u003cem\u003eProc. Natl. Acad. Sci. U. S. A.\u003c/em\u003e \u003cstrong\u003e115\u003c/strong\u003e, 12283\u0026ndash;12288 (2018).\u003c/li\u003e\n \u003cli\u003eSoares, S., Atallah, B. V. \u0026amp; Paton, J. J. Midbrain dopamine neurons control judgment of time. \u003cem\u003eScience (80-. ).\u003c/em\u003e \u003cstrong\u003e354\u003c/strong\u003e, 1273\u0026ndash;1277 (2016).\u003c/li\u003e\n \u003cli\u003ePastor, M. A., Artieda, J., Jahanshahi, M. \u0026amp; Obeso, J. A. Time estimation and reproduction is abnormal in parkinson\u0026rsquo;s disease. \u003cem\u003eBrain\u003c/em\u003e \u003cstrong\u003e115\u003c/strong\u003e, 211\u0026ndash;225 (1992).\u003c/li\u003e\n \u003cli\u003eHonma, M. \u003cem\u003eet al.\u003c/em\u003e Impaired cognitive modification for estimating time duration in Parkinson\u0026rsquo;s disease. \u003cem\u003ePLoS One\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, e0208956 (2018).\u003c/li\u003e\n \u003cli\u003eMagalh\u0026atilde;es, F. \u003cem\u003eet al.\u003c/em\u003e Neurochemical changes in basal ganglia affect time perception in parkinsonians. \u003cem\u003eJ. Biomed. Sci. 2018 251\u003c/em\u003e \u003cstrong\u003e25\u003c/strong\u003e, 1\u0026ndash;15 (2018).\u003c/li\u003e\n \u003cli\u003eCoull, J. T., Hwang, H. J., Leyton, M. \u0026amp; Dagher, A. Dopamine precursor depletion impairs timing in healthy volunteers by attenuating activity in putamen and supplementary motor area. \u003cem\u003eJ. Neurosci.\u003c/em\u003e \u003cstrong\u003e32\u003c/strong\u003e, 16704\u0026ndash;16715 (2012).\u003c/li\u003e\n \u003cli\u003eTomassini, A., Ruge, D., Galea, J. M., Penny, W. \u0026amp; Bestmann, S. The Role of Dopamine in Temporal Uncertainty. \u003cem\u003eJ. Cogn. Neurosci.\u003c/em\u003e \u003cstrong\u003e26\u003c/strong\u003e, 194\u0026ndash;198 (2016).\u003c/li\u003e\n \u003cli\u003eTanner, C. M. \u0026amp; Ostrem, J. L. Parkinson\u0026rsquo;s Disease. \u003cem\u003eN. Engl. J. Med.\u003c/em\u003e \u003cstrong\u003e391\u003c/strong\u003e, 442\u0026ndash;452 (2024).\u003c/li\u003e\n \u003cli\u003ePoewe, W. \u003cem\u003eet al.\u003c/em\u003e Parkinson disease. \u003cem\u003eNat. Rev. Dis. Prim.\u003c/em\u003e \u003cstrong\u003e3\u003c/strong\u003e, 1\u0026ndash;21 (2017).\u003c/li\u003e\n \u003cli\u003eRuitenberg, M. F. L., Duthoo, W., Santens, P., Notebaert, W. \u0026amp; Abrahamse, E. L. Sequential movement skill in Parkinson\u0026rsquo;s disease: A state-of-the-art. \u003cem\u003eCortex\u003c/em\u003e 102\u0026ndash;112 (2015) doi:10.1016/j.cortex.2015.01.005.\u003c/li\u003e\n \u003cli\u003eColautti, L., Iannello, P., Silveri, M. C. \u0026amp; Antonietti, A. Decision making in Parkinson\u0026rsquo;s disease: An analysis of the studies using the Iowa Gambling Task. \u003cem\u003eEur. J. Neurosci.\u003c/em\u003e \u003cstrong\u003e54\u003c/strong\u003e, 7513\u0026ndash;7549 (2021).\u003c/li\u003e\n \u003cli\u003eLe Heron, C., Morris, L.-A. \u0026amp; Manohar, S. Understanding disrupted motivation in Parkinson\u0026rsquo;s disease through a value-based decision-making lens. \u003cem\u003eTrends Neurosci.\u003c/em\u003e \u003cstrong\u003e48\u003c/strong\u003e, (2025).\u003c/li\u003e\n \u003cli\u003eSingh, A. \u003cem\u003eet al.\u003c/em\u003e Timing variability and midfrontal ~4 Hz rhythms correlate with cognition in Parkinson\u0026rsquo;s disease. \u003cem\u003enpj Park. Dis.\u003c/em\u003e \u003cstrong\u003e7\u003c/strong\u003e, 1\u0026ndash;8 (2021).\u003c/li\u003e\n \u003cli\u003eArtieda, J., Pastor, M. A., Lacruz, F. \u0026amp; Obeso, J. A. Temporal discrimination is abnormal in parkinson\u0026rsquo;s disease. \u003cem\u003eBrain\u003c/em\u003e \u003cstrong\u003e115\u003c/strong\u003e, 199\u0026ndash;210 (1992).\u003c/li\u003e\n \u003cli\u003eO\u0026rsquo;Boyle, D. J., Freeman, J. S. \u0026amp; Cody, F. W. J. The accuracy and precision of timing of self-paced, repetitive movements in subjects with Parkinson\u0026rsquo;s disease. \u003cem\u003eBrain\u003c/em\u003e \u003cstrong\u003e119\u003c/strong\u003e, 51\u0026ndash;70 (1996).\u003c/li\u003e\n \u003cli\u003eMalapani, C. \u003cem\u003eet al.\u003c/em\u003e Coupled Temporal Memories in Parkinson\u0026rsquo;s Disease: A Dopamine-Related Dysfunction. \u003cem\u003eJ. Cogn. Neurosci.\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e, 316\u0026ndash;331 (1998).\u003c/li\u003e\n \u003cli\u003eMalapani, C., Deweer, B. \u0026amp; Gibbon, J. Separating storage from retrieval dysfunction of temporal memory in Parkinson\u0026rsquo;s disease. \u003cem\u003eJ. Cogn. Neurosci.\u003c/em\u003e \u003cstrong\u003e14\u003c/strong\u003e, 311\u0026ndash;322 (2002).\u003c/li\u003e\n \u003cli\u003eMerchant, H., Zarco, W., Bartolo, R. \u0026amp; Prado, L. The Context of Temporal Processing Is Represented in the Multidimensional Relationships between Timing Tasks. \u003cem\u003ePLoS One\u003c/em\u003e \u003cstrong\u003e3\u003c/strong\u003e, e3169 (2008).\u003c/li\u003e\n \u003cli\u003eBrown, R. G. \u0026amp; Marsden, C. D. Cognitive function in Parkinson\u0026rsquo;s disease: From description to theory. \u003cem\u003eTrends Neurosci.\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 21\u0026ndash;29 (1990).\u003c/li\u003e\n \u003cli\u003eKehagia, A. A., Barker, R. A. \u0026amp; Robbins, T. W. Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson\u0026rsquo;s disease. \u003cem\u003eLancet Neurol.\u003c/em\u003e \u003cstrong\u003e9\u003c/strong\u003e, 1200\u0026ndash;1213 (2010).\u003c/li\u003e\n \u003cli\u003eRobbins, T. W. \u0026amp; Cools, R. Cognitive deficits in Parkinson\u0026rsquo;s disease: A cognitive neuroscience perspective. \u003cem\u003eMov. Disord.\u003c/em\u003e \u003cstrong\u003e29\u003c/strong\u003e, 597\u0026ndash;607 (2014).\u003c/li\u003e\n \u003cli\u003eBowes, S. G., O\u0026rsquo;nell, C. J. A., Dobbs, R. J., Dobrs, S. M. \u0026amp; Charlett, A. Bradyphrenia and Parkinsonism. \u003cem\u003eAge Ageing\u003c/em\u003e \u003cstrong\u003e23\u003c/strong\u003e, 1\u0026ndash;2 (1994).\u003c/li\u003e\n \u003cli\u003eSeveriano e Sousa, C. \u003cem\u003eet al.\u003c/em\u003e Profile of cognitive impairment in late-stage Parkinson\u0026rsquo;s disease. \u003cem\u003eBrain Behav.\u003c/em\u003e \u003cstrong\u003e12\u003c/strong\u003e, (2022).\u003c/li\u003e\n \u003cli\u003eWang, Y. X. \u003cem\u003eet al.\u003c/em\u003e Associations between cognitive impairment and motor dysfunction in Parkinson\u0026rsquo;s disease. \u003cem\u003eBrain Behav.\u003c/em\u003e \u003cstrong\u003e7\u003c/strong\u003e, e00719 (2017).\u003c/li\u003e\n \u003cli\u003ePereiro, A. X., Resu\u0026aacute;, B., Facal, D. \u0026amp; Cancela-Carral, J. M. Combining a Cognitive Concurrent Task with a Motor or Motor-Cognitive Task: Which Is Better to Differentiate Levels of Affectation in Parkinson\u0026rsquo;s Disease? \u003cem\u003ePark. Dis.\u003c/em\u003e \u003cstrong\u003e2020\u003c/strong\u003e, 2189084 (2020).\u003c/li\u003e\n \u003cli\u003eKann, S. J., Chang, C., Manza, P. \u0026amp; Leung, H. C. Akinetic rigid symptoms are associated with decline in a cortical motor network in Parkinson\u0026rsquo;s disease. \u003cem\u003enpj Park. Dis. 2020 61\u003c/em\u003e \u003cstrong\u003e6\u003c/strong\u003e, 1\u0026ndash;8 (2020).\u003c/li\u003e\n \u003cli\u003eAarsland, D. \u003cem\u003eet al.\u003c/em\u003e Parkinson disease-associated cognitive impairment. \u003cem\u003eNat. Rev. Dis. Prim. 2021 71\u003c/em\u003e \u003cstrong\u003e7\u003c/strong\u003e, 1\u0026ndash;21 (2021).\u003c/li\u003e\n \u003cli\u003eFraisse, P. Rhythm and tempo. in \u003cem\u003eThe Psychology of Music\u003c/em\u003e (ed. Academic, D. D. N. Y.) 149\u0026ndash;180 (1982).\u003c/li\u003e\n \u003cli\u003eWoodrow, H. Time Perception. \u003cem\u003eA Handb. Exp. Psychol.\u003c/em\u003e (1951).\u003c/li\u003e\n \u003cli\u003eGoetz, C. C. The Unified Parkinson\u0026rsquo;s Disease Rating Scale (UPDRS): Status and recommendations. \u003cem\u003eMov. Disord.\u003c/em\u003e \u003cstrong\u003e18\u003c/strong\u003e, 738\u0026ndash;750 (2003).\u003c/li\u003e\n \u003cli\u003eCoull, J. T. Neural correlates of attention and arousal: insights from electrophysiology, functional neuroimaging and psychopharmacology. \u003cem\u003eProg. Neurobiol. Vol.\u003c/em\u003e \u003cstrong\u003e55\u003c/strong\u003e, (1998).\u003c/li\u003e\n \u003cli\u003eCoull, J., Charras, P., Donadieu, M., Droit-Volet, S. \u0026amp; Vidal, F. SMA Selectively Codes the Active Accumulation of Temporal, Not Spatial, Magnitude. \u003cem\u003eJ Cogn Neurosci.\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e, 431\u0026ndash;441 (2015).\u003c/li\u003e\n \u003cli\u003eCoull, J. T., Vidal, F. \u0026amp; Burle, B. When to act, or not to act: That\u0026rsquo;s the SMA\u0026rsquo;s question. \u003cem\u003eCurr. Opin. Behav. Sci.\u003c/em\u003e \u003cstrong\u003e8\u003c/strong\u003e, 14\u0026ndash;21 (2016).\u003c/li\u003e\n \u003cli\u003eSantos, P. C. R. dos, Heimler, B., Koren, O., Flash, T. \u0026amp; Plotnik, M. Dopamine improves defective cortical and muscular connectivity during bilateral control of gait in Parkinson\u0026rsquo;s disease. \u003cem\u003eCommun. Biol.\u003c/em\u003e \u003cstrong\u003e7\u003c/strong\u003e, 1\u0026ndash;15 (2024).\u003c/li\u003e\n \u003cli\u003eDelgado-Alvarado, M., Ferrer-Gallardo, V. J., Paz-Alonso, P. M., Caballero-Gaudes, C. \u0026amp; Rodr\u0026iacute;guez-Oroz, M. C. Interactions between functional networks in Parkinson\u0026rsquo;s disease mild cognitive impairment. \u003cem\u003eSci. Reports 2023 131\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 1\u0026ndash;12 (2023).\u003c/li\u003e\n \u003cli\u003eVardy, Y., Bradshaw, J. L. \u0026amp; Iansek, R. Dual Target Identification and the Attentional Blink in Parkinson\u0026rsquo;s Disease. \u003cem\u003eJ. Clin. Exp. Neuropsychol.\u003c/em\u003e \u003cstrong\u003e25\u003c/strong\u003e, 361\u0026ndash;375 (2003).\u003c/li\u003e\n \u003cli\u003eRafal, R. D., Posner, M. I., Walker, J. A. \u0026amp; Friedrich, F. J. Cognition and the basal ganglia separating mental and motor components of performance in parkinson\u0026rsquo;s disease. \u003cem\u003eBrain\u003c/em\u003e \u003cstrong\u003e107\u003c/strong\u003e, 1083\u0026ndash;1094 (1984).\u003c/li\u003e\n \u003cli\u003eCools, R. Dopaminergic modulation of cognitive function-implications for L-DOPA treatment in Parkinson\u0026rsquo;s disease. \u003cem\u003eNeurosci. Biobehav. Rev.\u003c/em\u003e \u003cstrong\u003e30\u003c/strong\u003e, 1\u0026ndash;23 (2006).\u003c/li\u003e\n \u003cli\u003eRoy, M. A., Doiron, M., Talon-Croteau, J., Dupr\u0026eacute;, N. \u0026amp; Simard, M. Effects of Antiparkinson Medication on Cognition in Parkinson\u0026rsquo;s Disease: A Systematic Review. \u003cem\u003eCan. J. Neurol. Sci.\u003c/em\u003e \u003cstrong\u003e45\u003c/strong\u003e, 375\u0026ndash;404 (2018).\u003c/li\u003e\n \u003cli\u003eLiu, C., Goel, P. \u0026amp; Kaeser, P. S. Spatial and temporal scales of dopamine transmission. \u003cem\u003eNat. Rev. Neurosci. 2021 226\u003c/em\u003e \u003cstrong\u003e22\u003c/strong\u003e, 345\u0026ndash;358 (2021).\u003c/li\u003e\n \u003cli\u003eShen, W., Flajolet, M., Greengard, P. \u0026amp; Surmeier, D. J. Dichotomous dopaminergic control of striatal synaptic plasticity. \u003cem\u003eScience (80-. ).\u003c/em\u003e \u003cstrong\u003e321\u003c/strong\u003e, 848\u0026ndash;851 (2008).\u003c/li\u003e\n \u003cli\u003eDotov, D. G. \u003cem\u003eet al.\u003c/em\u003e Biologically-variable rhythmic auditory cues are superior to isochronous cues in fostering natural gait variability in Parkinson\u0026rsquo;s disease. \u003cem\u003eGait Posture\u003c/em\u003e \u003cstrong\u003e51\u003c/strong\u003e, 64\u0026ndash;69 (2017).\u003c/li\u003e\n \u003cli\u003eHove, M. J., Suzuki, K., Uchitomi, H., Orimo, S. \u0026amp; Miyake, Y. Interactive Rhythmic Auditory Stimulation Reinstates Natural 1/f Timing in Gait of Parkinson\u0026rsquo;s Patients. \u003cem\u003ePLoS One\u003c/em\u003e \u003cstrong\u003e7\u003c/strong\u003e, e32600 (2012).\u003c/li\u003e\n \u003cli\u003eDuppen, C. P. \u003cem\u003eet al.\u003c/em\u003e Blending motor learning approaches for short-term adjustments to gait in people with Parkinson disease. \u003cem\u003eExp. Brain Res.\u003c/em\u003e \u003cstrong\u003e242\u003c/strong\u003e, 2853\u0026ndash;2863 (2024).\u003c/li\u003e\n \u003cli\u003eBella, S. D., Benoit, C. E., Farrugia, N., Schwartze, M. \u0026amp; Kotz, S. A. Effects of musically cued gait training in Parkinson\u0026rsquo;s disease: Beyond a motor benefit. \u003cem\u003eAnn. N. Y. Acad. Sci.\u003c/em\u003e \u003cstrong\u003e1337\u003c/strong\u003e, 77\u0026ndash;85 (2015).\u003c/li\u003e\n \u003cli\u003eBenoit, C. E. \u003cem\u003eet al.\u003c/em\u003e Musically cued gait-training improves both perceptual and motor timing in Parkinson\u0026rsquo;s disease. \u003cem\u003eFront. Hum. Neurosci.\u003c/em\u003e \u003cstrong\u003e8\u003c/strong\u003e, 1\u0026ndash;11 (2014).\u003c/li\u003e\n \u003cli\u003eThaut, M. H. \u003cem\u003eet al.\u003c/em\u003e Rhythmic auditory stimulation in gait training for Parkinson\u0026rsquo;s disease patients. \u003cem\u003eMov. Disord.\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 193\u0026ndash;200 (1996).\u003c/li\u003e\n \u003cli\u003eMcintosh, G. C., Brown, S. H., Rice, R. R. \u0026amp; Thaut, M. H. patterns in patients with Parkinson \u0026rsquo; s disease. \u003cem\u003eJ. Neurol. Neurosurg. Psychiatry\u003c/em\u003e 22\u0026ndash;26 (1997).\u003c/li\u003e\n \u003cli\u003eFrank, M. J., Seeberger, L. C. \u0026amp; O\u0026rsquo;Reilly, R. C. By carrot or by stick: cognitive reinforcement learning in parkinsonism. \u003cem\u003eScience (80-. ).\u003c/em\u003e \u003cstrong\u003e306\u003c/strong\u003e, 1940\u0026ndash;3 (2004).\u003c/li\u003e\n \u003cli\u003eVan Nuland, A. J. \u003cem\u003eet al.\u003c/em\u003e Effects of dopamine on reinforcement learning in Parkinson\u0026rsquo;s disease depend on motor phenotype. \u003cem\u003eBrain\u003c/em\u003e \u003cstrong\u003e143\u003c/strong\u003e, 3422\u0026ndash;3434 (2021).\u003c/li\u003e\n \u003cli\u003eMaquet, P. The role of sleep in learning and memory. \u003cem\u003eScience (80-. ).\u003c/em\u003e \u003cstrong\u003e294\u003c/strong\u003e, 1048\u0026ndash;1052 (2001).\u003c/li\u003e\n \u003cli\u003eGirardeau, G. \u0026amp; Lopes-Dos-Santos, V. Brain neural patterns and the memory function of sleep. \u003cem\u003eScience (80-. ).\u003c/em\u003e \u003cstrong\u003e374\u003c/strong\u003e, 560\u0026ndash;564 (2021).\u003c/li\u003e\n \u003cli\u003eKleiner, M. \u003cem\u003eet al.\u003c/em\u003e What \u0026rsquo; s new in Psychtoolbox-3 ? (2007).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7301023/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7301023/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAuditory periodic temporal attention is a fundamental rhythmic process that operates optimally around 1.5 Hz. Synchronized rhythmic movements further enhance its efficacy. This link between movement and timing is thought to rely on the subcortical basal ganglia dopamine pathway, which is crucial for both motor functions and temporal processing. However, whether dopamine underpins the relationship between auditory temporal attention and motor activity remains unclear. Using an auditory temporal attention task with Parkinsonian patients either ON or OFF the dopaminergic medication L-DOPA and healthy controls, we found that dopamine does not modulate the optimal sampling rate of auditory temporal attention, at 1.5 Hz. However, dopamine enables motor synchronization to the auditory stream and is hence crucial for the motor benefits of auditory temporal attention. Finally, early dopaminergic support is necessary to consolidate performance improvements across sessions. These findings underscore a selective role for dopamine in audio-motor interaction, while suggesting that the intrinsic rhythm of auditory attention is dopamine-independent.\u003c/p\u003e","manuscriptTitle":"Dopamine modulation of motor and implicit learning contributions to auditory temporal attention","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-01 08:43:00","doi":"10.21203/rs.3.rs-7301023/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"55969d8f-1407-4115-8e8f-ff696bcf5209","owner":[],"postedDate":"September 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":53338596,"name":"Biological sciences/Neuroscience/Cognitive neuroscience/Attention"},{"id":53338597,"name":"Biological sciences/Psychology/Human behaviour"},{"id":53338598,"name":"Biological sciences/Neuroscience/Diseases of the nervous system/Parkinson's disease"}],"tags":[],"updatedAt":"2025-10-06T20:40:30+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-01 08:43:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7301023","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7301023","identity":"rs-7301023","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}