Auditory prediction cues motor preparation in the absence of movements.

There is increasing evidence for integrated representation of sensory and motor information in the brain, and that seeing or hearing action-related stimuli may automatically cue the movements required to respond to or produce them. In this study we tested whether anticipation of tones in a known melody automatically activates corresponding motor representations in a predictive way, in preparation for potential upcoming movements. Therefore, we trained 20 non-musicians (8 men, 12 women) to play a simple melody. Then, while they passively listened to the learned or unlearned melodies, we applied single pulse transcranial magnetic stimulation (TMS) over M1 to measure motor evoked potentials from the associated finger muscle either preceding or following the onset of individual tones. Our results show that listening to the learned melody increased corticospinal excitability for specific finger muscles before tone onset. This demonstrates that predictable auditory information can activate motor representations in an anticipatory muscle-specific manner, even in the absence of intention to move. This suggests that the motor system is involved in the prediction of sensory events, likely based on auditory-parietal-prefrontal feedforward/feedback loops that automatically prepare predictable sound-related actions independent of actual execution and the associated auditory feedback. Overall, we propose that multimodal forward models of upcoming sounds and actions support motor preparation, facilitate error detection and correction, and guide perception.

Testing the Role of Dorsal Premotor Cortex in Auditory-Motor Association Learning Using Transcranical Magnetic Stimulation (TMS).

Interactions between the auditory and the motor systems are critical in music as well as in other domains, such as speech. The premotor cortex, specifically the dorsal premotor cortex (dPMC), seems to play a key role in auditory-motor integration, and in mapping the association between a sound and the movement used to produce it. In the present studies we tested the causal role of the dPMC in learning and applying auditory-motor associations using 1 Hz repetitive Transcranical Magnetic Stimulation (rTMS). In this paradigm, non-musicians learn a set of auditory-motor associations through melody training in two contexts: first when the sound to key-press mapping was in a conventional sequential order (low to high tones mapped onto keys from left to right), and then when it was in a novel scrambled order. Participant's ability to match the four pitches to four computer keys was tested before and after the training. In both experiments, the group that received 1 Hz rTMS over the dPMC showed no significant improvement on the pitch-matching task following training, whereas the control group (who received rTMS to visual cortex) did. Moreover, in Experiment 2 where the pitch-key mapping was novel, rTMS over the dPMC also interfered with learning. These findings suggest that rTMS over dPMC disturbs the formation of auditory-motor associations, especially when the association is novel and must be learned rather explicitly. The present results contribute to a better understanding of the role of dPMC in auditory-motor integration, suggesting a critical role of dPMC in learning the link between an action and its associated sound.

Melodic Priming of Motor Sequence Performance: The Role of the Dorsal Premotor Cortex.

The purpose of this study was to determine whether exposure to specific auditory sequences leads to the induction of new motor memories and to investigate the role of the dorsal premotor cortex (dPMC) in this crossmodal learning process. Fifty-two young healthy non-musicians were familiarized with the sound to key-press mapping on a computer keyboard and tested on their baseline motor performance. Each participant received subsequently either continuous theta burst stimulation (cTBS) or sham stimulation over the dPMC and was then asked to remember a 12-note melody without moving. For half of the participants, the contour of the melody memorized was congruent to a subsequently performed, but never practiced, finger movement sequence (Congruent group). For the other half, the melody memorized was incongruent to the subsequent finger movement sequence (Incongruent group). Hearing a congruent melody led to significantly faster performance of a motor sequence immediately thereafter compared to hearing an incongruent melody. In addition, cTBS speeded up motor performance in both groups, possibly by relieving motor consolidation from interference by the declarative melody memorization task. Our findings substantiate recent evidence that exposure to a movement-related tone sequence can induce specific, crossmodal encoding of a movement sequence representation. They further suggest that cTBS over the dPMC may enhance early offline procedural motor skill consolidation in cognitive states where motor consolidation would normally be disturbed by concurrent declarative memory processes. These findings may contribute to a better understanding of auditory-motor system interactions and have implications for the development of new motor rehabilitation approaches using sound and non-invasive brain stimulation as neuromodulatory tools.

Transcranial Direct Current Stimulation for the Treatment of Chronic Tinnitus: A Randomized Controlled Study.

BACKGROUND: Tinnitus is an often disabling condition for which there is no effective therapy. Current research suggests that tinnitus may develop due to maladaptive plastic changes and altered activity in the auditory and prefrontal cortex. Transcranial direct current stimulation (tDCS) modulates brain activity and has been shown to transiently suppress tinnitus in trials. OBJECTIVE: To investigate the efficacy and safety of tDCS in the treatment of chronic subjective tinnitus. METHODS: In a randomized, parallel, double-blind, sham-controlled study, the efficacy and safety of cathodal tDCS to the auditory cortex with anode over the prefrontal cortex was investigated in five sessions over five consecutive days. Tinnitus was assessed after the last session on day 5, and at follow-up visits 1 and 3 months post stimulation using the Tinnitus Handicap Inventory (THI, primary outcome measure), Subjective Tinnitus Severity Scale, Hospital Anxiety and Depression scale, Visual Analogue Scale, and Clinical Global Impression scale. RESULTS: 42 patients were investigated, 21 received tDCS and 21 sham stimulation. There were no beneficial effects of tDCS on tinnitus as assessed by primary and secondary outcome measures. Effect size assessed with Cohen's d amounted to 0.08 (95% CI: -0.52 to 0.69) at 1 month and 0.18 (95% CI: -0.43 to 0.78) at 3 months for the THI. CONCLUSION: tDCS of the auditory and prefrontal cortices is safe, but does not improve tinnitus. Different tDCS protocols might be beneficial.

Crossmodal encoding of motor sequence memories.

In this study, we tested the hypothesis that exposure to specific auditory sequences could lead to the crossmodal induction of new motor memories. Twenty young, healthy participants memorized a melody without moving. Each tone in the memorized melody had previously been associated with a particular finger movement. For ten of the participants, the contour of the melody memorized was congruent to a subsequently performed, but never practiced, finger movement sequence (C group, n = 10). For the other ten participants, the melody memorized was incongruent to the subsequent finger movement sequence (InC group, n = 10). Results showed faster performance of the movement sequence in the C group than in the InC group. This difference in motor performance was most pronounced 6 h after melody learning and then dissipated over 30 days. These results provide evidence of a specific, crossmodal encoding of a movement sequence representation through an auditory sequence with the effect on motor performance lasting for several hours. The findings of this study are significant, as the formation of new motor memories through exposure to auditory stimuli may be useful in rehabilitation settings where the initial encoding of motor memories through physical training is disrupted.

Implicit task sequence learning in patients with Parkinson's disease, frontal lesions and amnesia: the critical role of fronto­striatal loops.

The purpose of this study was to investigate the role of the fronto­striatal system for implicit task sequence learning. We tested performance of patients with compromised functioning of the fronto­striatal loops, that is, patients with Parkinson's disease and patients with lesions in the ventromedial or dorsolateral prefrontal cortex. We also tested amnesic patients with lesions either to the basal forebrain/orbitofrontal cortex or to thalamic/medio-temporal regions. We used a task sequence learning paradigm involving the presentation of a sequence of categorical binary-choice decision tasks. After several blocks of training, the sequence, hidden in the order of tasks, was replaced by a pseudo-random sequence. Learning (i.e., sensitivity to the ordering) was assessed by measuring whether this change disrupted performance. Although all the patients were able to perform the decision tasks quite easily, those with lesions to the fronto­striatal loops (i.e., patients with Parkinson's disease, with lesions in the ventromedial or dorsolateral prefrontal cortex and those amnesic patients with lesions to the basal forebrain/orbitofrontal cortex) did not show any evidence of implicit task sequence learning. In contrast, those amnesic patients with lesions to thalamic/medio-temporal regions showed intact sequence learning. Together, these results indicate that the integrity of the fronto­striatal system is a prerequisite for implicit task sequence learning.

Resting tremor in Parkinson disease: a negative predictor of levodopa-induced dyskinesia.

BACKGROUND: It is unclear whether patients with different clinical subtypes of Parkinson disease (PD) differ in their risk of developing levodopa-induced dyskinesia (LID) and whether resting tremor is negatively correlated with this risk. OBJECTIVES: To determine whether resting tremor as an initial manifestation of PD negatively correlated with subsequent occurrence and severity of LID and to study the correlations between LID and other epidemiological factors (eg, age at onset of PD and duration of PD). DESIGN: Logistic regression analysis was used to determine predictive factors of LID. Spearman rank correlations between LID and epidemiological factors and motor signs (including tremor) were calculated. SETTING: Institutional tertiary referral center for movement disorders. PATIENTS: Cohort of 85 patients with PD. MAIN OUTCOME MEASURE: Occurrence of LID according to the Unified Parkinson Disease Rating Scale part IV. RESULTS: Resting tremor as an initial manifestation of PD was associated with reduced risk of developing LID independent of other predictors of LID (duration of PD, axial signs, and levodopa dose). CONCLUSION: Resting tremor as an initial manifestation of PD predicts lower probability of developing LID under levodopa treatment.

Motor sequence learning performance in Parkinson's disease patients depends on the stage of disease.

It is still unclear, whether patients with Parkinson's disease (PD) are impaired in the incidental learning of different motor sequences in short succession, although such a deficit might greatly impact their daily life. The aim of this study was thus to clarify the relation between disease parameters of PD and incidental motor learning of two different sequences in short succession. Results revealed that the PD patients were able to acquire two sequences in short succession but needed more time than healthy subjects. However, both the severity of axial manifestations, as assessed on a subsection of the Unified Parkinson's Disease Rating Scale III (UPDRS III) and the Hoehn and Yahr score, and the levodopa-equivalent dose (LED) were negatively correlated with the sequence learning performance. These findings indicate that, although PD patients are able to learn two sequences in short succession, they need more time and their overall sequence learning performance is strongly correlated with the stage of disease.

Is there a recognition memory deficit in Parkinson's disease? Evidence from estimates of recollection and familiarity.

There is conflicting evidence whether Parkinson's disease (PD) is associated with impaired recognition memory and which of its underlying processes, namely recollection and familiarity, is more affected by the disease. The present study explored the contribution of recollection and familiarity to verbal recognition memory performance in 14 nondemented PD patients and a healthy control group with two different methods: (i) the word-frequency mirror effect, and (ii) Remember/Know judgments. Overall, recognition memory of patients was intact. The word-frequency mirror effect was observed both in patients and controls: Hit rates were higher and false alarm rates were lower for low-frequency compared to high-frequency words. However, Remember/Know judgments indicated normal recollection, but impaired familiarity. Our findings suggest that mild to moderate PD patients are selectively impaired at familiarity whereas recollection and overall recognition memory are intact.

Interference during the implicit learning of two different motor sequences.

It has been demonstrated that learning a second motor task after having learned a first task may interfere with the long-term consolidation of the first task. However, little is known about immediate changes in the representation of the motor memory in the early acquisition phase within the first minutes of the learning process. Therefore, we investigated such early interference effects with an implicit serial reaction time task in 55 healthy subjects. Each subject performed either a sequence learning task involving two different sequences, or a random control task. The results showed that learning the first sequence led to only a slight, short-lived interference effect in the early acquisition phase of the second sequence. Overall, learning of neither sequence was impaired. Furthermore, the two processes, sequence-unrelated task learning (i.e. general motor training) and the sequence learning itself did not appear to interfere with each other. In conclusion, although the long-term consolidation of a motor memory has been shown to be sensitive to other interfering memories, the present study suggests that the brain is initially able to acquire more than one new motor sequence within a short space of time without significant interference.