Neural Basis of Long-term Musical Memory in Cognitively Impaired Older Persons.

OBJECTIVE: The objective of this study was to determine whether exposure to long-known music would evoke more extensive activation of brain regions minimally affected by Alzheimer disease (AD) pathology and outside traditional memory networks using a functional magnetic resonance imaging paradigm involving listening to long-known and recently-learned music in older adults with cognitive impairment to provide insight into mechanisms of long-term musical memory preservation in cognitively impaired older persons. METHODS: Seventeen subjects with a diagnosis of mild AD or mild cognitive impairment were recruited for this study. Subjects were scanned using functional magnetic resonance imaging while they performed a music listening task, which included short clips of personally selected music from the patient's past and newly-composed music heard for the first time 60 minutes before scanning. From this task, we obtained group-level maps comparing brain areas associated with long-known and recently-heard music in all subjects. RESULTS: Exposure to long-known music preferentially activated brain regions including the medial prefrontal cortex, precuneus, anterior insula, basal ganglia, hippocampus, amygdala, and cerebellum relative to recently-heard music. These areas are involved in autobiographical memory and associated emotional responses. In addition, they are minimally affected by early stage AD pathology, thus providing a neural basis for long-known musical memory survival. CONCLUSIONS: Long-known music activates a bilateral network of prefrontal, emotional, motor, auditory, and subcortical regions (cerebellum, putamen, limbic structures). This extensive activation, relative to recently-heard music, may offer structural and functional clues as to why long-term musical memory appears to be relatively preserved among cognitively impaired older persons.

The neural bases of familiar music listening in healthy individuals: An activation likelihood estimation meta-analysis.

Accumulating evidence suggests that the neural activations during music listening differs as a function of familiarity with the excerpts. However, the implicated brain areas are unclear. After an extensive literature search, we conducted an Activation Likelihood Estimation analysis on 23 neuroimaging studies (232 foci, 364 participants) to identify consistently activated brain regions when healthy adults listen to familiar music, compared to unfamiliar music or an equivalent condition. The results revealed a left cortical-subcortical co-activation pattern comprising three significant clusters localized to the supplementary motor areas (BA 6), inferior frontal gyrus (IFG, BA 44), and the claustrum/insula. Our results are discussed in a predictive coding framework, whereby temporal expectancies and familiarity may drive motor activations, despite any overt movement. Though conventionally associated with syntactic violation, our observed activation in the IFG may support a recent proposal of its involvement in a network that subserves both violation and prediction. Finally, the claustrum/insula plays an integral role in auditory processing, functioning as a hub that integrates sensory and limbic information to (sub)cortical structures.

Music-based intervention drives paretic limb acceleration into intentional movement frequencies in chronic stroke rehabilitation.

This study presented a novel kinematic assessment of paretic limb function "online" during the actual therapeutic exercisers rooted within the acceleration domain. Twenty-eight patients at chronic stroke stages participated in an auditory-motor intervention mapping reaching movements of the paretic arm unto surfaces of large digital musical instruments and sound tablets that provided rhythmic entrainment cues and augmented auditory feedback. Patients also wore a tri-axial accelerometer on the paretic limb during the nine-session intervention. The resulting acceleration profiles were extracted and quantified within the frequency domain. Measures of peak power and peak width were leveraged to estimate volitional control and temporal consistency of paretic limb movements, respectively. Clinical assessments included the Wolf Motor Function Test and Fugl-Meyer - Upper Extremity subtest. The results showed that peak power increased significantly from Session 1 to Session 9 within oscillatory frequency ranges associated with intentional movement execution (i.e., 4.5 Hz). Decreases in peak width over time provided additional evidence for improved paretic arm control from a temporal perspective. In addition, Peak width values obtained in Session 1 was significantly correlated with pre-test Fugl-Meyer - Upper Extremity scores. These results highlighted improvements in paretic limb acceleration as an underlying mechanism in stroke motor recovery and shed further light on the utility of accelerometry-based measures of paretic limb control in stroke rehabilitation. The data reported here was obtained from a larger clinical trial: https://clinicaltrials.gov/ct2/show/NCT03246217 ClinicalTrials.gov Identifier: NCT03246217.

Therapeutic Instrumental Music Training and Motor Imagery in Post-Stroke Upper-Extremity Rehabilitation: A Randomized-Controlled Pilot Study.

OBJECTIVE: To investigate the potential benefits of 3 therapeutic instrumental music performance (TIMP)-based interventions in rehabilitation of the affected upper-extremity (UE) for adults with chronic poststroke hemiparesis. DESIGN: Randomized-controlled pilot study. SETTING: University research facility. PARTICIPANTS: Community-dwelling volunteers (N=30; 16 men, 14 women; age range, 33-76 years; mean age, 55.9 years) began and completed the protocol. All participants had sustained a unilateral stroke more than 6 months before enrollment (mean time poststroke, 66.9 months). INTERVENTION: Two baseline assessments, a minimum of 1 week apart; 9 intervention sessions (3 times/week for 3 weeks), in which rhythmically cued, functional arm movements were mapped onto musical instruments; and 1 post-test following the final intervention. Participants were block-randomized to 1 of 3 conditions: group 1 (45 minutes TIMP), group 2 (30 minutes TIMP, 15 minutes metronome-cued motor imagery [TIMP+cMI]), and group 3 (30 minutes TIMP, 15 minutes motor imagery without cues [TIMP+MI]). Assessors and investigators were blinded to group assignment. MAIN OUTCOME MEASURES: Fugl-Meyer Upper-Extremity (FM-UE) and Wolf Motor Function Test- Functional Ability Scale (WMFT-FAS). Secondary measures were motor activity log (MAL)-amount of use scale and trunk impairment scale. RESULTS: All groups made statistically significant gains on the FM-UE (TIMP, P=.005, r=.63; TIMP+cMI, P=.007, r=.63; TIMP+MI, P=.007, r=.61) and the WMFT-FAS (TIMP, P=.024, r=.53; TIMP+cMI, P=.008, r=.60; TIMP+MI, P=.008, r=.63). Comparing between-group percent change differences, on the FM-UE, TIMP scored significantly higher than TIMP+cMI (P=.032, r=.57), but not TIMP+MI. There were no differences in improvement on WMFT-FAS across conditions. On the MAL, gains were significant for TIMP (P=.030, r=.54) and TIMP+MI (P=.007, r=.63). CONCLUSION: TIMP-based techniques, with and without MI, led to significant improvements in paretic arm control on primary outcomes. Replacing a physical training segment with imagery-based training resulted in similar improvements; however, synchronizing internal and external cues during auditory-cMI may pose additional sensorimotor integration challenges.

Long-Known Music Exposure Effects on Brain Imaging and Cognition in Early-Stage Cognitive Decline: A Pilot Study.

BACKGROUND: Repeated exposure to long-known music has been shown to have a beneficial effect on cognitive performance in patients with AD. However, the brain mechanisms underlying improvement in cognitive performance are not yet clear. OBJECTIVE: In this pilot study we propose to examine the effect of repeated long-known music exposure on imaging indices and corresponding changes in cognitive function in patients with early-stage cognitive decline. METHODS: Participants with early-stage cognitive decline were assigned to three weeks of daily long-known music listening, lasting one hour in duration. A cognitive battery was administered, and brain activity was measured before and after intervention. Paired-measures tests evaluated the longitudinal changes in brain structure, function, and cognition associated with the intervention. RESULTS: Fourteen participants completed the music-based intervention, including 6 musicians and 8 non-musicians. Post-baseline there was a reduction in brain activity in key nodes of a music-related network, including the bilateral basal ganglia and right inferior frontal gyrus, and declines in fronto-temporal functional connectivity and radial diffusivity of dorsal white matter. Musician status also significantly modified longitudinal changes in functional and structural brain measures. There was also a significant improvement in the memory subdomain of the Montreal Cognitive Assessment. CONCLUSION: These preliminary results suggest that neuroplastic mechanisms may mediate improvements in cognitive functioning associated with exposure to long-known music listening and that these mechanisms may be different in musicians compared to non-musicians.

Relationship Between Cognition and Gait at 2- and 12-Months Post-Traumatic Brain Injury.

Background: A common and debilitating challenge experienced by people with TBI is gait-associated mobility impairment and persisting cognitive impairments. Cognitive and physical impairments are often addressed independently during rehabilitation, however, increasing evidence links cognitive and motor processes more closely. Objectives: (1) To determine if correlations exist between measures of cognitive and gait recovery, post-TBI. (2) To investigate the predictive power of cognition at 2-months on gait outcomes at 12-months post-TBI. Methods: In this secondary, longitudinal study of cognitive and neural recovery, data from 93 participants admitted to an inpatient neurorehabilitation program were analyzed. Spatiotemporal gait variables [velocity, step time variability (STV), step length variability (SLV)] were collected along with cognitive variables [Trail Making Test-B (TMT-B), Digit Span-Forward (DS-F)]. Spearman's correlation coefficients were calculated between gait and cognitive variables. Multilinear and step wise regression analyses were calculated to determine predictive value of cognitive variables at 2-months on gait performance at 12-months-post TBI. Results: At 2-months post-injury, TMT-B was significantly correlated with gait velocity and STV; and DS-F was significantly correlated with velocity. At 12-months post-injury, TMT-B and DS-F was still significant correlated with velocity. TMT-B at 2-months was correlated with SLV and STV at 12-months; and DS-F correlated significantly with velocity. Regression models showed TMT-B at 2-months predicting STV, SLV, and velocity at 12-months. Conclusions: Significant associations and predictions between physical and cognitive recovery post-TBI were observed in this study. Future directions may consider a "neural internetwork" model as a salient rehabilitation approach in TBI that integrates physical and cognitive functions.

Effects of therapeutic instrumental music performance and motor imagery on chronic post-stroke cognition and affect: A randomized controlled trial.

BACKGROUND: The burden of post-stroke cognitive impairment, as well as affective disorders, remains persistently high. With improved stroke survival rates and increasing life expectancy, there is a need for effective interventions to facilitate remediation of neurocognitive impairments and post-stroke mood disorders. OBJECTIVE: To investigate the effects of Therapeutic Instrumental Music Performance (TIMP) training with and without Motor Imagery on cognitive functioning and affective responding in chronic post-stroke individuals. METHODS: Thirty chronic post-stroke, community-dwelling participants were randomized to one of three experimental arms: (1) 45 minutes of active TIMP, (2) 30 minutes of active TIMP followed by 15 minutes of metronome-cued motor imagery (TIMP+cMI), (3) 30 minutes of active TIMP followed by 15 minutes of motor imagery without cues (TIMP+MI). Training took place three times a week for three weeks, using a selection of acoustic and electronic instruments. Assessments, administered at two baselines and post-training, included the Trail Making Test (TMT) - Part B to assess mental flexibility, the Digit Span Test (DST) to determine short-term memory capacity, the Multiple Affect Adjective Checklist - Revised (MAACL-R) to ascertain current affective state, and the General Self-Efficacy Scale (GSE) to assess perceived self-efficacy. The Self-Assessment Maniqin (SAM) was also administered prior to and following each training session. RESULTS: Thirty participants completed the protocol, ten per arm [14 women; mean age = 55.9; mean time post-stroke = 66.9 months]. There were no statistically significant differences between pooled group baseline measures. The TIMP+MI group showed a statistically significant decrease in time from pre-test 2 to post-test on the TMT. The TIMP group showed a significant increase on MAACL sensation seeking scores, as well as on the Valence and Dominance portions of the SAM; TIMP+cMI showed respective increases and decreases in positive and negative affect on the MAACL, and increases on the Valence, Dominance, and Arousal portions of the SAM. No statistically significant association between cognitive and affective measures was obtained. CONCLUSIONS: The mental flexibility aspect of executive functioning appears to be enhanced by therapeutic instrumental music training in conjunction with motor imagery, possibly due to multisensory integration and consolidation of representations through motor imagery rehearsal following active practice. Active training using musical instruments appears to have a positive impact on affective responding; however, these changes occurred independently of improvements to cognition.

Development and evaluation of a novel music-based therapeutic device for upper extremity movement training: A pre-clinical, single-arm trial.

Restoration of upper limb motor function and patient functional independence are crucial treatment targets in neurological rehabilitation. Growing evidence indicates that music-based intervention is a promising therapeutic approach for the restoration of upper extremity functional abilities in neurologic conditions such as cerebral palsy, stroke, and Parkinson's Disease. In this context, music technology may be particularly useful to increase the availability and accessibility of music-based therapy and assist therapists in the implementation and assessment of targeted therapeutic goals. In the present study, we conducted a pre-clinical, single-arm trial to evaluate a novel music-based therapeutic device (SONATA) for upper limb extremity movement training. The device consists of a graphical user interface generated by a single-board computer displayed on a 32" touchscreen with built-in speakers controlled wirelessly by a computer tablet. The system includes two operational modes that allow users to play musical melodies on a virtual keyboard or draw figures/shapes whereby every action input results in controllable sensory feedback. Four motor tasks involving hand/finger movement were performed with 21 healthy individuals (13 males, aged 26.4 ± 3.5 years) to evaluate the device's operational modes and main features. The results of the functional tests suggest that the device is a reliable system to present pre-defined sequences of audiovisual stimuli and shapes and to record response and movement data. This preliminary study also suggests that the device is feasible and adequate for use with healthy individuals. These findings open new avenues for future clinical research to further investigate the feasibility and usability of the SONATA as a tool for upper extremity motor function training in neurological rehabilitation. Directions for future clinical research are discussed.

Effects of Rhythmic Sensory Stimulation on Ehlers-Danlos Syndrome: A Pilot Study.

Ehlers-Danlos syndrome (EDS) is a connective tissue disorder characterized by joint hypermobility and skin extensibility and is often accompanied by chronic pain. Rhythmic sensory stimulation (RSS) can be defined as the stimulation of the senses in a periodic manner within a range of low frequencies. Music plus sound delivered through a vibroacoustic device is a form of RSS and has demonstrated utility in managing pain. In this current study, we conducted an open-label pilot study of 15 patients with hypermobile EDS using RSS as the intervention. Posttreatment improvements were seen in 11 of the 15 patients (73%), whereas 3 of the 15 patients (20%) experienced worse outcomes. Of the 14 patients that completed the experiment, 6 participants (43%) were classified as "responders" to the device while 8 participants (57%) were classified as "nonresponders." Responders demonstrated significant improvements in pain interference (51.5 ± 16 preintervention vs. 43.5 ± 16.4 postintervention BPI score) and depression symptoms (34.0 ± 15.9 preintervention vs. 26.8 ± 12.1 postintervention CESD score). Poststudy interviews confirm the improvements of pain interference, mood, and bowel symptoms. Furthermore, analysis of medical conditions within the responder group indicates that the presence of depression, anxiety, irritable bowel syndrome, and fibromyalgia may indicate a greater likelihood for patients to benefit with vibroacoustic applications. These results indicate a possible potential for RSS, delivered using a vibroacoustic device, in managing pain-related symptoms. Further research is necessary to elucidate the exact mechanism behind the physiological benefits of RSS.