According to World health organization, stroke accounts as the third main cause of disability across the world (1). The incidence of stroke related disability have almost doubled in the developing countries in the past decade (2, 3). The disability affects basic day to day life activities (4), which further increase dependency (5), anxiety, depression (6), social isolation (7), and promote a poor quality of life (8, 9). Moreover, the disability inflicts substantial economic burden on patients (10).
Typically, patients affected from stroke exhibit sensorimotor dysfunctions on the contralateral side of the affected brain region (11). These deficits can be exhibited focally, segmentally, unilaterally, or bilaterally (12). The symptoms are typically characterized by progressive inefficient movement synergy patterns (13), abnormal muscle tone (14), force production (15), compromised dexterity (16), poor coordination (17), and more (18). Moreover, hyper/hypokinetic movement disorders are also common [see Handley et al.,(12)]. Additionally, cognitive and sensory dysfunctions are also common in patients with stroke (19). Despite advancements in rehabilitation, poor prognosis in stroke is still prevalent, especially for recovering arm function (5, 20). Studies suggest that upper limb recovery is an important predictor for determining the health status outcome, and quality of life for stroke patients (21, 22).
The poor gross and fine motor performance in upper extremities can be due to abnormal co-contraction of antagonists/agonists (23), disruptions in force production/adaptation (24), and regulation of stretch reflex (15, 25). Besides, these musculoskeletal dysfunctions can considerably impair joint kinematics (26, 27). According to Hara et al. (28) impaired activation of motor units in terms of firing rate and synchronization might result in such deficits. Furthermore, as the disease progresses, these changes increase fatigue (29), reduce coordination (30), and with the progression of time promote development of joint contractures (31), and subluxations/dislocations (32). Likewise, discrepancies in sensory perceptions, memory, cognition, and behavior further impact the prognostic outcome of a stroke patient (33–35).
Neuroimaging studies suggest site specific lesions and silent infarcts at medial temporal lobe (36), gray (37), and white matter (38), further leading to a wide array of cognitive dysfunctions (39) [see Makin, (40) and Sperber and Karnath (41).] Similarly, deficits in corticospinal (42, 43), thalamocortical (44), superior occipito-frontal (41), and superior-longitudinal pathways (45), might overload the already impaired cognitive-motor pathways. Such a constraining impact on the impaired cognitive pathways might increase “internal” conscious monitoring by the patients to control their movements [see movement re-investment 46–48)]. This increase in attention is aimed to safeguard the stability of a movement (49, 50), it retrospectively impairs autonomic execution of a movement and promotes movement failure (46–48). Likewise, dysfunctions in sensory perception could affect perceptuomotor representations in the brain, thereby affecting motor planning and execution (35). Together, these cognitive and sensorimotor dysfunctions affect the prognosis of a stroke patient.
Common treatment strategies to curb cognitive motor dysfunctions in stroke patients include training with virtual-reality (51), mental imagery (52), biofeedback (53), physical therapy (54), exercise (55), prosthesis (56–58), dual-task priority training, and more (59). Recently studies have tried to enhance the stroke recovery by simultaneously addressing the sensory deficits with motor rehabilitation by applying external sensory stimulation as a neuro-prosthetic (59–62). Studies have analyzed the effects of different sensory stimuli in auditory, visual and tactile domain on motor performance (59, 61, 62). However, the literature predominantly supports the beneficial role of auditory stimuli (50, 63, 64). The main reasons which underlie the beneficial effects are thought to be multifaceted. Firstly, rich neuroanatomical interconnectivity has been reported between auditory and motor cortex (65–67). Here, inference can be drawn from literature evaluating auditory startle reflex on animal models (68, 69). Studies using Double-labeling experiments have revealed that cochlear root neurons in the auditory nerve can project bilaterally to sensorimotor paths, including synapsing on reticulospinal neurons (65, 68, 70). Likewise, patterns of thalamocortical and corticocortical inputs unique to auditory cortex have also been reported [for a detailed review see (71)]. In humans, neuroimaging data confirms the presence of cortico-subcortical network involving putamen, supplementary motor area, premotor cortex, and the auditory cortex especially for perceiving and processing rhythmic auditory stimuli (72–75). Secondly, the human auditory system can consistently perceive auditory cues 20–50 ms faster as compared to its visual and tactile counterparts (76–78). Thirdly, the auditory system has a strong bias to identify temporal patterns of periodicity and structure as compared to other sensory perceptual systems (78–80). For instance, auditory rhythmic perception has been reported to exist well beyond the limits of temporal resolution of visual modalities i.e., when periodicities are presented at a rate of ~300–900 ms (80, 81).
In the literature, however, rhythmic auditory cueing (67), and real-time kinematic auditory feedback (82), also termed as sonification, are the most widely studied approaches in upper limb stroke rehabilitation. Both the methods possess differential influence over neurophysiological and musculoskeletal domains. Firstly, rhythmic auditory cueing can be defined as repetitive isosynchronous stimulations applied with an aim to simultaneously synchronize motor execution (83, 84). Here, neuroimaging data for rhythmic auditory stimuli suggests facilitated activations in premotor cortex, insula, cuneus, supplementary motor area, cerebellum, and basal ganglia (73, 80, 85–87). Moreover, training with rhythmic auditory cueing has been reported to modulate neuromagnetic β oscillations (88, 89), biological motion perception (82, 90), auditory-motor imagery (91–93), shape variability in musculoskeletal activation patterns (94), cortical reorganization, neural-plasticity (95, 96), and also movement specific re-investment (97). Real-time kinematic auditory feedback on the other hand is a comparatively new approach. Such type of an intervention involves mapping of movement parameters on to the sound components, such as pitch, amplitude with a very minimal or no latency (82). The feedback has been reported to alleviate sensory perceptions like proprioception (98), by enhancing sensorimotor representation while facilitating activations in action observation system (90), and inducing neural plasticity (99). Moreover, the feedback has been reported by Effenberg et al. (82) to extend the benefits of discrete rhythmic auditory cueing stimuli. Here, the authors suggest that the continuous flow of information might allow a participant to better perceive their movement amplitudes and positioning, thereby resulting in development of both feedback and feed-forward models (82). Moreover, by allowing additional influence over the action observation system the real-time auditory stimuli might also enrich the internal stimulation of the executed movement (50, 82, 90). This methodology involves delivering action relevant auditory feedback, where the characteristics of stimuli (e.g., frequency, amplitude) are mapped to the specific joint kinematics in real-time, for an example see (98). Schmitz et al. (90) in a neuroimaging study reported that observation of a convergent audio (sonification)-visual feedback led to enhanced activations in fronto-parietal networks, action observation system i.e., superior temporal sulcus, Broadman area 44, 6, insula, precentral gyrus, cerebellum, thalamus and basal ganglia (90). The authors mentioned that the multimodal nature of the stimuli can enhance the activation in areas associated with biological motion perception and in sub-cortical structures involving striatal-thalamic frontal motor loop. This then might improve perceptual analysis of a movement thereby resulting in efficient motor planning and execution (90).
Till date, no study has analyzed the influence of real-time auditory feedback on upper limb recovery post-stroke. Moreover, no study has compared the influence of rhythmic and real-time auditory stimuli on upper limb recovery post stroke. This information might serve to be an important source of information for future research and for developing efficient rehabilitation protocols in stroke community. Only four systematic reviews have analyzed the influence of rhythmic auditory stimulations on arm recovery post stroke (100, 101–103), in which only two reviews included a statistical meta-analysis (102, 103). In these studies limitations persisted in terms of meta-analysis approach i.e., no heterogeneity analysis. Therefore, interpretation of results from the statistical analyses might indicate biasing. Therefore, the aim of the present systematic review and meta-analysis is to develop a state of knowledge where both qualitative and quantitative data for different auditory stimuli delivery methods can be interpreted for the use of stroke patients and medical practitioners alike. Moreover, a meta-analysis approach will be used to determine specific training dosage for auditory stimuli in recovering arm function post-stroke.[…]