[Sensorimotor synchronization and non-verbal behaviors in Alzheimer's disease: the influence of social and musical context]. / Synchronisation sensorimotrice et comportements non verbaux dans la maladie d'Alzheimer : l'influence du contexte social et musical.

BACKGROUND: Considering the limited efficacy of pharmacological treatments, the use of musical interventions as non-drug treatment for patients with Alzheimer's disease are strongly recommended. Musical interventions seem to improve the socio-emotional and cognitive functioning of these patients, with benefits increasing when patients are engaged at the motor level. OBJECTIVE: Our study evaluates the factors that may influence patients' socio-emotional and motor engagement during musical activities, and measures their sensorimotor synchronization (SMS) abilities. METHODS: Each participant was asked to tap with a metronomic or a musical rhythm, in the presence of a musician who performed the task with them. The presence of the musician was real (live condition) or virtual (video condition). Two tempi were tested: a slow tempo (inter-onset interval of 800 ms) and a fast tempo (inter-onset interval of 667 ms). RESULTS: Patients spontaneously produced more rhythmic movements in response to the music than to the metronome. However, the consistency and accuracy of sensorimotor synchronization were better with the metronome than with the music, and also better in video than in live condition. These effects were modulated by the tempo of the auditory sequences. CONCLUSION: These results confirm the importance of the musical context and social interactions on these different performances. By evaluating in parallel the hand sensorimotor synchronization, spontaneous motor and socio-emotional behaviors with quantitative and controlled measurements, this study validates a multimodal approach to evaluate the patients' engagement in a musical task. These initial results open up promising application prospects while providing clinicians and researchers a rigorous methodology for understanding the factors that are at the origin of the therapeutic benefits of musical activities on the behavior and well-being of patients and their caregivers.

Exogenous orienting of attention in hearing: a virtual reality paradigm to assess auditory attention in neglect patients.

While mechanisms of orienting attention in unilateral spatial neglect (USN) have frequently been studied in the visual domain, these mechanisms remain relatively unexplored in the auditory domain. Our first goal was to replicate Spence and Driver's (J Exp Psychol Hum 22:1005-1030, 1994) results with a virtual reality paradigm. This paradigm simulated a 3-dimensional auditory space with headphones. Our second aim was to study auditory profiles of orienting attention in USN. In a first experiment, 18 healthy participants performed an auditory cueing spatial paradigm (either a target-detection task or a target-lateralization task). In a second experiment, 14 right-stroke patients (10 with USN and 4 without USN) performed these two same tasks. As in Spence and Driver's (J Exp Psychol Hum 22:1005-1030, 1994), our first experiment showed that spatial representations are not utilized for the detection of auditory stimuli. However, during the lateralization task, participants were quicker to detect targets preceded by a spatially congruent cue, which suggests that our paradigm could be suitable for studying orienting attention in hearing. Our second experiment found that patients with USN also needed an explicit spatial task to be sensitive to auditory spatial cueing. In the target-lateralization task, they showed effects lateralized only to one side of space, whereas patients without USN did not. Although our paradigm needs replications to better understand orienting attention impairments in hearing in USN, this study could have implications for the development of clinical tasks that could assess auditory spatial attention in USN syndrome.

Auditory lateralisation deficits in neglect patients.

Although visual deficits due to unilateral spatial neglect (USN) have been frequently described in the literature, fewer studies have been interested in directional hearing impairment in USN. The aim of this study was to explore sound lateralisation deficits in USN. Using a paradigm inspired by Tanaka et al. (1999), interaural time differences (ITD) were presented over headphones to give the illusion of a leftward or a rightward movement of sound. Participants were asked to respond "right" and "left" as soon as possible to indicate whether they heard the sound moving to the right or to the left side of the auditory space. We additionally adopted a single-case method to analyse the performance of 15 patients with right-hemisphere (RH) stroke and added two additional measures to underline sound lateralisation on the left side and on the right side. We included 15 patients with RH stoke (5 with a severe USN, 5 with a mild USN and 5 without USN) and 11 healthy age-matched participants. We expected to replicate findings of abnormal sound lateralisation in USN. However, although a sound lateralisation deficit was observed in USN, two different deficit profiles were identified. Namely, patients with a severe USN seemed to have left sound lateralisation impairment whereas patients with a mild USN seemed to be more influenced by a systematic bias in auditory representation with respect to body meridian axis (egocentric deviation). This latter profile was unexpected as sounds were manipulated with ITD and, thus, would not be perceived as coming from an external source of the head. Future studies should use this paradigm in order to better understand these two distinct profiles.

The feeling of familiarity for music in patients with a unilateral temporal lobe lesion: A gating study.

Previous research has indicated that the medial temporal lobe (MTL), and more specifically the perirhinal cortex, plays a role in the feeling of familiarity for non-musical stimuli. Here, we examined contribution of the MTL to the feeling of familiarity for music by testing patients with unilateral MTL lesions. We used a gating paradigm: segments of familiar and unfamiliar musical excerpts were played with increasing durations (250, 500, 1000, 2000, 4000 ms and complete excerpts), and participants provided familiarity judgments for each segment. Based on the hypothesis that patients might need longer segments than healthy controls (HC) to identify excerpts as familiar, we examined the onset of the emergence of familiarity in HC, patients with a right MTL resection (RTR), and patients with a left MTL resection (LTR). In contrast to our hypothesis, we found that the feeling of familiarity was relatively spared in patients with a right or left MTL lesion, even for short excerpts. All participants were able to differentiate familiar from unfamiliar excerpts as early as 500 ms, although the difference between familiar and unfamiliar judgements was greater in HC than in patients. These findings suggest that a unilateral MTL lesion does not impair the emergence of the feeling of familiarity. We also assessed whether the dynamics of the musical excerpt (linked to the type and amount of information contained in the excerpts) modulated the onset of the feeling of familiarity in the three groups. The difference between familiar and unfamiliar judgements was greater for high than for low-dynamic excerpts for HC and RTR patients, but not for LTR patients. This indicates that the LTR group did not benefit in the same way from dynamics. Overall, our results imply that the recognition of previously well-learned musical excerpts does not depend on the integrity of either right or the left MTL structures. Patients with a unilateral MTL resection may compensate for the effects of unilateral damage by using the intact contralateral temporal lobe. Moreover, we suggest that remote semantic memory for music might depend more strongly on neocortical structures rather than the MTL.

Efficacy of musical interventions in dementia: methodological requirements of nonpharmacological trials.

The management of patients with Alzheimer's disease is a significant public health problem given the limited effectiveness of pharmacological therapies combined with iatrogenic effects of drug treatments in dementia. Consequently, the development of nondrug care, such as musical interventions, has become a necessity. The experimental rigor of studies in this area, however, is often lacking. It is therefore difficult to determine the impact of musical interventions on patients with dementia. As part of a series of studies, we carried out randomized controlled trials to compare the effectiveness of musical activities to other pleasant activities on various functions in patients with severe Alzheimer's disease. The data obtained in these trials are discussed in light of the methodological constraints and requirements specific to these clinical studies. Although the results demonstrate the power of music on the emotional and behavioral status of patients, they also suggest that other pleasant activities (e.g., cooking) are also effective, leaving open the question about the specific benefits of music in patients with dementia. All these findings highlight the promising potential for nonpharmacological treatments to improve the well-being of patients living in residential care and to reduce caregiver burden.

An Intracranial EEG Study of the Neural Dynamics of Musical Valence Processing.

The processing of valence is known to recruit the amygdala, orbitofrontal cortex, and relevant sensory areas. However, how these regions interact remains unclear. We recorded cortical electrical activity from 7 epileptic patients implanted with depth electrodes for presurgical evaluation while they listened to positively and negatively valenced musical chords. Time-frequency analysis suggested a specific role of the orbitofrontal cortex in the processing of positively valenced stimuli while, most importantly, Granger causality analysis revealed that the amygdala tends to drive both the orbitofrontal cortex and the auditory cortex in theta and alpha frequency bands, during the processing of valenced stimuli. Results from the current study show the amygdala to be a critical hub in the emotion processing network: specifically one that influences not only the higher order areas involved in the evaluation of a stimulus's emotional value but also the sensory cortical areas involved in the processing of its low-level acoustic features.

Intracranial markers of emotional valence processing and judgments in music.

The involvement of the amygdala and orbitofrontal cortex in the processing of valenced stimuli is well established. However, less is known about the extent to which activity in these regions reflects a stimulus' physical properties, the individual subjective experience it evokes, or both. We recorded cortical electrical activity from five epileptic patients implanted with depth electrodes for presurgical evaluation while they rated "consonant" and "dissonant" musical chords using a "pleasantness" scale. We compared the pattern of responses in the amygdala and orbitofrontal cortex when trials were sorted by pleasantness judgments relative to when they were sorted by the acoustic properties known to influence emotional reactions to musical chords. This revealed earlier differential activity in the amygdala in the physical properties-based, relative to in the judgment-based, analyses. Thus, our results demonstrate that the amygdala has, first and foremost, a high initial sensitivity to the physical properties of valenced stimuli. The finding that differentiations in the amygdala based on pleasantness ratings had a longer latency suggests that in this structure, mediation of emotional judgment follows accumulation of sensory information. This is in contrast to the orbitofrontal cortex where sensitivity to sensory information did not precede differentiation based on affective judgments.

Efficacy of musical interventions in dementia: evidence from a randomized controlled trial.

Although musical interventions have recently gained popularity as a non-pharmacological treatment in dementia, there is still insufficient evidence of their effectiveness. To investigate this issue, a single-center randomized controlled trial was conducted with forty-eight patients with Alzheimer's disease or mixed dementia to compare the effects of music versus cooking interventions in the emotional, cognitive, and behavioral domain, as well as on professional caregiver distress. Each intervention lasted four weeks (two one-hour sessions a week). Multi-component evaluations (with blind assessors) were conducted before, during, and after the interventions to assess their short and long-term effects (up to four weeks post interventions). Analyses revealed that both music and cooking interventions led to positive changes in the patients' emotional state and decreased the severity of their behavioral disorders, as well as reduced caregiver distress. However, no benefit on the cognitive status of the patients was seen. While results did not demonstrate a specific benefit of music on any of the considered measures, the present study suggests the efficacy of two pleasant non-pharmacological treatments in patients with moderate to severe dementia. Our findings highlight the potential of such interventions in improving the well-being of patients living in residential care, as well as reducing caregiver distress.

An overview of the use of music therapy in the context of Alzheimer's disease: a report of a French expert group.

OBJECTIVES: The aim of this overview is to present the developments of music therapy in France, its techniques, mechanisms and principal indications, mainly in the context of Alzheimer's disease. METHODS: An international review of the literature on music therapy applied to Alzheimer's disease was conducted using the principal scientific search engines. A work group of experts in music therapy and psychosocial techniques then considered the different points highlighted in the review of literature and discussed them. RESULTS AND DISCUSSION: Clinical and neurophysiological studies have enlightened some positive benefits of music in providing support for people with Alzheimer's disease or related disorders. Music therapy acts mainly through emotional and psycho-physiological pathways. It includes a series of techniques that can respond to targeted therapeutic objectives. Some studies have shown that music therapy reduces anxiety, alleviates periods of depression and aggressive behaviour and thus significantly improves mood, communication and autonomy of patients. CONCLUSION: Psychosocial interventions, such as music therapy, can contribute to maintain or rehabilitate functional cognitive and sensory abilities, as well as emotional and social skills and to reduce the severity of some behavioural disorders.

[Non pharmacological treatment for Alzheimer's disease: comparison between musical and non-musical interventions]. / Thérapies non médicamenteuses dans la maladie d'Alzheimer : comparaison d'ateliers musicaux et non musicaux.

On account of the limited effectiveness of pharmacological treatments in Alzheimer's disease (AD), there is a growing interest on nonpharmacological treatments, including musical intervention. Despite the large number of studies showing the multiple benefits of music on behavioral, emotional and cognitive disorders of patients with AD, only a few of them used a rigorous method. Finally, the specificity of musical as compared to non-musical and pleasant interventions has rarely been addressed. To investigate this issue, two randomized controlled trials were conducted contrasting the effects of musical to painting (Study 1) or cooking (Study 2) interventions on emotional state of 33 patients with AD. The patients' emotional state was assessed by analyzing professional caregivers' judgments of the patient's mood, then facial expressions and valence of the discourse from short-filmed interviews. In the first study (n=22), each intervention lasted 3 weeks (two sessions per week) and the patients' emotional state was assessed before, during and after intervention periods. After the interventions, the results showed that facial expression, discourse content and mood assessment improved (more positive than negative expressions) as compared to pre-intervention assessment. However, musical intervention was more effective and had longer effects as compared with painting. In the second study (n=11), we further examined long lasting effects of music as compared to cooking by adding evaluation of the patients' emotional state 2 and 4 weeks after the last intervention. Again, music was more effective to improve the emotional state. Music had positive effects that remained significant up to 4 weeks after the intervention, while cooking only produced short-term effect on mood. In both studies, benefits were significant in more than 80% of patients. Taken together, these findings show that music intervention has specific effects on patients' emotional well being, offering promising methods to improve the quality of life of patients with AD.

The relationship of lyrics and tunes in the processing of unfamiliar songs: a functional magnetic resonance adaptation study.

The cognitive relationship between lyrics and tunes in song is currently under debate, with some researchers arguing that lyrics and tunes are represented as separate components, while others suggest that they are processed in integration. The present study addressed this issue by means of a functional magnetic resonance adaptation paradigm during passive listening to unfamiliar songs. The repetition and variation of lyrics and/or tunes in blocks of six songs was crossed in a 2 x 2 factorial design to induce selective adaptation for each component. Reductions of the hemodynamic response were observed along the superior temporal sulcus and gyrus (STS/STG) bilaterally. Within these regions, the left mid-STS showed an interaction of the adaptation effects for lyrics and tunes, suggesting an integrated processing of the two components at prelexical, phonemic processing levels. The degree of integration decayed toward more anterior regions of the left STS, where the lack of such an interaction and the stronger adaptation for lyrics than for tunes was suggestive of an independent processing of lyrics, perhaps resulting from the processing of meaning. Finally, evidence for an integrated representation of lyrics and tunes was found in the left dorsal precentral gyrus (PrCG), possibly relating to the build-up of a vocal code for singing in which musical and linguistic features of song are fused. Overall, these results demonstrate that lyrics and tunes are processed at varying degrees of integration (and separation) through the consecutive processing levels allocated along the posterior-anterior axis of the left STS and the left PrCG.

Cerebral mechanisms of prosodic sensory integration using low-frequency bands of connected speech.

Even if speech perception has been reported to involve both left and right hemispheres, converging data have posited the existence of a functional asymmetry at the level of secondary auditory cortices. Using fMRI in 12 right-handed French men listening passively to long connected speech stimuli, we addressed the question of neuronal networks involved in the integration of low frequency bands of speech by comparing 1) differences in brain activity in two listening conditions (FN, NF) differing in the integration of pitch modulations (in FN, low frequencies, obtained by a low-pass filter, are addressed to the left ear while the whole acoustic message is simultaneously addressed to the right ear, NF being the reverse position); 2) differences in brain activity induced by high and low degrees of prosodic expression (expressive vs. flat); and 3) effects of the same connected speech stimulus in the two listening conditions. Each stimulus induced a specific cerebral network, the flat one weakening activations which were mainly reduced to the bilateral STG for both listening conditions. In the expressive condition, the specific sensory integration FN results in an increase of the articulatory loop and new recruitments such as right BA6-44, left BA39-40, the left posterior insula and the bilateral BA30. This finding may be accounted for by the existence of temporal windows differing both in length and in acoustic cues decoding, strengthening the "asymmetric sampling in time" hypothesis posited by Poeppel (Speech Commun 2003; 41:245-255). Such an improvement of prosodic integration could find applications in the rehabilitation of some speech disturbances.

Cerebral mechanisms of prosodic integration: evidence from connected speech.

Using functional Magnetic Resonance Imaging (fMRI) and long connected speech stimuli, we addressed the question of neuronal networks involved in prosodic integration by comparing (1) differences in brain activity when hearing connected speech stimuli with high and low degrees of prosodic expression; (2) differences in brain activity in two different diotic listening conditions (normal speech delivery to both ears, i.e., NN; and low-pass-filtered speech delivery to both ears, i.e., FF); and (3) effects of high and low degrees of prosodic information in the NN and FF conditions. Twelve right-handed French men listened passively to the stimuli. Each stimulus induced a specific cerebral network, the flat one weakening activations, which were mainly reduced to the bilateral STG for both listening conditions. High degrees of prosodic information were found to trigger right specific activations in a wider neuronal network involved in speech integration (such as BA44, BA21-22 and BA39-40) than low degrees of prosodic information did. More precisely, the right BA44 was found to be specifically involved in the process of F(0) modulations, which are the main acoustic correlate of prosody. Not only do the results achieved in the present experiment using 30-s-long connected speech stimuli show the involvement of a bilateral neuronal network but they also strongly suggest that high degrees of prosodic information elicit activations in a wider neuronal network involved in speech perception than low degrees of prosodic information do.