Socio-emotional and motor engagement during musical activities in older adults with major neurocognitive impairment.

Although music therapy may engender clinical benefits in patients with neurodegenerative disease, the impacts of social and musical factors of such activities on socio-emotional and motor engagements are poorly understood. To address this issue, non-verbal behaviors of 97 patients with or without major cognitive impairment (CI) were assessed when listening to music or a metronome in front of a musician who was present physically (live) or virtually (video). Socio-emotional engagement was quantified as emotional facial expression production and gaze direction. Motor engagement was quantified as overall body motion and the production of rhythmic movements. In both groups, positive facial expressions were more frequent and rhythmic motor activities lasted longer with music than with a metronome, and during a live performance rather than a video performance. Relative to patients without CI, patients with CI moved less with music, expressed fewer emotions, and spent less time looking at the musician in the video condition and in the metronome condition. The relative reductions in motor and socio-emotional engagements in patients with CI might be markers of disease progression. However, the presence of a live partner induces older adults to engage emotionally and physically in musical activities emphasizing the relevance of using live performance as motivational levers during music therapy.

Does a Live Performance Impact Synchronization to Musical Rhythm in Cognitively Impaired Elderly?

BACKGROUND: Music-based interventions appear to be efficient approaches to improve emotional, social, and cognitive functioning of patients with neurodegenerative diseases. OBJECTIVE: Because benefits seem to increase with patient's motor involvement, we studied sensorimotor synchronization (SMS) abilities of patients with cognitive impairments (Alzheimer's disease, vascular and mixed dementia) and of patients with no evidence of cognitive impairments. More specifically, we compared the impact of a live performance by a musician to a video recording on SMS. METHODS: SMS to a metronomic or a musical stimulus was assessed while patients watched a live musician or his pre-recorded video. RESULTS: SMS to a metronome was better than to music but this effect was modulated by the social context. While SMS to a metronome was better when facing a video than a live performance, there was no impact of social context on SMS to music. No group differences of SMS were found. CONCLUSION: The decrease in SMS to a metronome in a live performance may be due to social pressure. Such a pressure might be removed in pleasant social activities, like moving with music in a group, explaining the lack of effect on SMS to music. We found no performance differences in groups, suggesting relatively spared SMS in cognitively impaired patients. By showing that it is possible to encourage patients to synchronize with others, even when facing a video, our results indicate that SMS can be used as a relevant predictor in clinical trials and open up promising therapeutic options for isolated patients.

[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.

Interictal epileptic discharge correlates with global and frontal cognitive dysfunction in temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) with hippocampal sclerosis has widespread effects on structural and functional connectivity and often entails cognitive dysfunction. EEG is mandatory to disentangle interactions in epileptic and physiological networks which underlie these cognitive comorbidities. Here, we examined how interictal epileptic discharges (IEDs) affect cognitive performance. METHODS: Thirty-four patients (right TLE=17, left TLE=17) were examined with 24-hour video-EEG and a battery of neuropsychological tests to measure intelligence quotient and separate frontal and temporal lobe functions. Hippocampal segmentation of high-resolution T1-weighted imaging was performed with FreeSurfer. Partial correlations were used to compare the number and distribution of clinical interictal spikes and sharp waves with data from imagery and psychological tests. RESULTS: The number of IEDs was negatively correlated with executive functions, including verbal fluency and intelligence quotient (IQ). Interictal epileptic discharge affected cognitive function in patients with left and right TLE differentially, with verbal fluency strongly related to temporofrontal spiking. In contrast, IEDs had no clear effects on memory functions after corrections with partial correlations for age, age at disease onset, disease duration, and hippocampal volume. CONCLUSION: In patients with TLE of long duration, IED occurrence was strongly related to cognitive deficits, most pronounced for frontal lobe function. These data suggest that IEDs reflect dysfunctional brain circuitry and may serve as an independent biomarker for cognitive comorbidity.

Neural correlates of binding lyrics and melodies for the encoding of new songs.

Songs naturally bind lyrics and melody into a unified representation. Using a subsequent memory paradigm, we examined the neural processes associated with binding lyrics and melodies during song encoding. Participants were presented with songs in two conditions: a unified condition (melodies sung with lyrics), and a separate condition (melodies sung with the syllable "la"). In both cases, written lyrics were displayed and participants were instructed to memorize them by repeating them covertly or by generating mental images of the songs. We expected the unified condition to recruit the posterior superior temporal gyrus, known to be involved in perceptual integration of songs, as well as the left inferior frontal gyrus (IFG). Conversely, we hypothesized that the separate condition would engage a larger network including the hippocampus to bind lyrics and melodies of songs, and the basal ganglia and the cerebellum to ensure the correct sequence coupling of verbal and musical information in time. Binding lyrics and melodies in the unified condition revealed activation of the left IFG, bilateral middle temporal gyrus (MTG), and left motor cortex, suggesting a strong linguistic processing for this condition. Binding in the separate compared to the unified condition revealed greater activity in the right hippocampus as well as other areas including the left caudate, left cerebellum, and right IFG. This study provides novel evidence for the role of the right hippocampus in binding lyrics and melodies in songs. Results are discussed in light of studies of binding in the visual domain and highlight the role of regions involved in timing and synchronization such as the basal ganglia and the cerebellum.

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.

Hippocampal-thalamic wiring in medial temporal lobe epilepsy: Enhanced connectivity per hippocampal voxel.

OBJECTIVE: Medial temporal lobe epilepsy (TLE) with hippocampal sclerosis is often accompanied by widespread changes in ipsilateral and contralateral white matter connectivity. Recent studies have proposed that patients may show pathologically enhanced wiring of the limbic circuits. To better address this issue, we specifically probed connection patterns between hippocampus and thalamus and examined their impact on cognitive function. METHODS: A group of 44 patients with TLE (22 with right and 22 with left hippocampal sclerosis) and 24 healthy control participants were examined with high-resolution T1 imaging, memory functional magnetic resonance imaging (fMRI) and probabilistic diffusion tractography. Thirty-four patients had further extensive neuropsychological testing. After whole brain segmentation with FreeSurfer, tractography streamline samples were drawn with hippocampus as the seed and thalamus as the target region. Two tractography strategies were applied: The first targeted the anatomic thalamic volume segmented in FreeSurfer and the second a functional region of interest in the mediodorsal thalamus derived from the activation during delayed recognition memory. RESULTS: We found a pronounced enhancement of connectivity between the sclerotic hippocampus and the ipsilateral thalamus both in the right and left TLE as compared to healthy control participants. This finding held for both the anatomically and the functionally defined thalamic target. Although differences were apparent in the number of absolute fibers, they were most pronounced when correcting for hippocampal volume. In terms of cognitive function, the number of hippocampal-thalamic connections was negatively correlated with performance in a variety of executive tasks, notably in the Trail Making Test, thus suggesting that the pathologic wiring did not compensate cognitive curtailing. SIGNIFICANCE: We suggest that TLE is accompanied by an abnormal and dysfunctional enhancement of connectivity between the hippocampus and the thalamus, which is maximal on the side of the sclerosis. This pathologic pattern of limbic wiring might reflect structural remodeling along common pathways of seizure propagation.

Facial, vocal and musical emotion recognition is altered in paranoid schizophrenic patients.

Disturbed processing of emotional faces and voices is typically observed in schizophrenia. This deficit leads to impaired social cognition and interactions. In this study, we investigated whether impaired processing of emotions also affects musical stimuli, which are widely present in daily life and known for their emotional impact. Thirty schizophrenic patients and 30 matched healthy controls evaluated the emotional content of musical, vocal and facial stimuli. Schizophrenic patients are less accurate than healthy controls in recognizing emotion in music, voices and faces. Our results confirm impaired recognition of emotion in voice and face stimuli in schizophrenic patients and extend this observation to the recognition of emotion in musical stimuli.

Music and dementia.

There is an increasing incidence of dementia in our aging population, and consequently an urgent need to develop treatments and activities that may alleviate the symptoms of dementia. Accumulating evidence shows that persons with dementia enjoy music, and their ability to respond to music is potentially preserved even in the late or severe stages of dementia when verbal communication may have ceased. Media interest in this topic has contributed to the public perception that music abilities are an "island of preservation" in an otherwise cognitively impaired person with dementia. In this chapter, we review the current literature on music cognition in dementia and show that there has been very scarce rigorous scientific investigation of this issue, and that various types of music memory exist and are differentially impaired in the different types of dementia. Furthermore, we discuss the recent development of music activities as a nonpharmacological treatment for dementia and highlight the methodological limitations of the current literature on this topic. While it has been reported that music activities can improve behavior, (particularly agitation), mood, and cognition in persons with dementia, recent large-scale randomized control studies have questioned the specificity of the effect of music and found that it is no more beneficial than other pleasant activities. Nevertheless, music is unique in its powerful ability to elicit both memories and emotions. This can provide an important link to individual's past and a means of nonverbal communication with carers, which make it an ideal stimulus for persons with dementia.

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.

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.

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.

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.

[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.

Agnosic or semantic impairment in very mild Alzheimer's disease?

The present study investigated object recognition impairment and the existence of category effects in patients with mild Alzheimer's disease. A battery of tests was designed to assess the deterioration of semantic memory and/or the existence of agnosia by evaluating visual and auditory naming, knowledge of structural descriptions (pre-semantic representation of an object within each perceptual system) and conceptual knowledge. The group of Alzheimer's patients were impaired in all experimental tests as compared to healthy participants. This result suggests an impairment of multiple levels of object integration processing even at an early stage of the disease. The patients also demonstrated a category effect with massive difficulties in recognizing human actions and musical instruments as compared to the other categories. This study provides an innovative clinical tool for exploring the recognition of visual and auditory objects at different levels of representation, allowing for the description of early signs of Alzheimer disease.

The effect of musical experience on emotional self-reports and psychophysiological responses to dissonance.

To study the influence of musical education on emotional reactions to dissonance, we examined self-reports and physiological responses to dissonant and consonant musical excerpts in listeners with low (LE: n=15) and high (HE: n=13) musical experience. The results show that dissonance induces more unpleasant feelings and stronger physiological responses in HE than in LE participants, suggesting that musical education reinforces aversion to dissonance. Skin conductance (SCR) and electromyographic (EMG) signals were analyzed according to a defense cascade model, which takes into account two successive time windows corresponding to orienting and defense responses. These analyses suggest that musical experience can influence the defense response to dissonance and demonstrate a powerful role of musical experience not only in autonomic but also in expressive responses to music.

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.

Auditory/visual duration bisection in patients with left or right medial-temporal lobe resection.

Patients with unilateral (left or right) medial temporal lobe lesions and normal control (NC) volunteers participated in two experiments, both using a duration bisection procedure. Experiment 1 assessed discrimination of auditory and visual signal durations ranging from 2 to 8 s, in the same test session. Patients and NC participants judged auditory signals as longer than equivalent duration visual signals. The difference between auditory and visual time discrimination was equivalent for the three groups, suggesting that a unilateral temporal lobe resection does not modulate the modality effect. To document interval-timing abilities after temporal lobe resection for different duration ranges, Experiment 2 investigated the discrimination of brief, 50-200 ms, auditory durations in the same patients. Overall, patients with right temporal lobe resection were found to have more variable duration judgments across both signal modality and duration range. These findings suggest the involvement of the right temporal lobe at the level of the decision process in temporal discriminations.

Impaired recognition of scary music following unilateral temporal lobe excision.

Music constitutes an ideal means to create a sense of suspense in films. However, there has been minimal investigation into the underlying cerebral organization for perceiving danger created by music. In comparison, the amygdala's role in recognition of fear in non-musical contexts has been well established. The present study sought to fill this gap in exploring how patients with amygdala resection recognize emotional expression in music. To this aim, we tested 16 patients with left (LTR; n = 8) or right (RTR; n = 8) medial temporal resection (including amygdala) for the relief of medically intractable seizures and 16 matched controls in an emotion recognition task involving instrumental music. The musical selections were purposely created to induce fear, peacefulness, happiness and sadness. Participants were asked to rate to what extent each musical passage expressed these four emotions on 10-point scales. In order to check for the presence of a perceptual problem, the same musical selections were presented to the participants in an error detection task. None of the patients was found to perform below controls in the perceptual task. In contrast, both LTR and RTR patients were found to be impaired in the recognition of scary music. Recognition of happy and sad music was normal. These findings suggest that the anteromedial temporal lobe (including the amygdala) plays a role in the recognition of danger in a musical context.

Effect of unilateral temporal lobe resection on short-term memory for auditory object and sound location.

To investigate auditory spatial and nonspatial short-term memory, a sound location discrimination task and an auditory object discrimination task were used in patients with medial temporal lobe resection. The results showed a double dissociation between the side of the medial temporal lobe lesion and the nature of the auditory discrimination deficits, suggesting that right and left temporal lobe structures are differently involved in auditory spatial and nonspatial short-term memory.