Neurological diseases are often associated with several behavioral and psychological symptoms that are usually overlooked by neurologists because require diagnostic methods that differ from those used for classical somatic symptoms and are more suitable to the field of psychiatry. On the other hand, psychiatrists do not seem to give an adequate attention to these symptoms considering them as a consequence of a cerebral damage and more pertinent to neurologists. This clinical attitude is historically based on the obsolete and reductive distinction between “organic” and “functional” behavioral disorders introduced by the phrenologist George Combe in 19^th century. According to Combe, cerebral diseases were respectively classified depending on the presence or the absence of cerebral lesions and from that time on this terminology has been used to indicate that some behavioral disorders are linked to a neurological damage while others are not. However, the reductionism of Combe’s distinction clearly emerges from the clinical observation given that a wide range of nervous system’s illnesses with different etiology shows both neurological and psychiatric symptoms. Emotional and behavioral disturbances with a polymorphic symptomatology are often connected to neurological disorders such as Multiple Sclerosis (MS)[1-3], Parkinson’s Disease (PD)[4], stroke[5], dementia[6], traumatic brain injury[7], epilepsy[8,9], Amyotrophic Lateral Sclerosis (ALS) and others Motor Neuron Diseases (MND)[10,11], pain syndromes (like headaches) and can be observed even with or without “organic” neurological diseases, thus miming in some cases an idiopathic psychiatric disorder.

Most common psychiatric disorders in neurology are depression, anxiety, maniacal states, and thought and perception disorders. Other psychiatric syndromes that can be seen in persons with neurological disorders are alexithymia, worry, and locus of control[12]. For example, mood disorders are often associated with acute or chronic cerebrovascular pathologies where the most common complications is certainly depression, usually defined post-stroke depression (PSD). The frequency of this syndrome is variable accordingly to different studies with a mean of 40% of the cases[13] and data obtained by numerous studies seem to indicate the presence of multiple etiological factors, both structural-endogenous and environmental-external, that may change depending on the early or late onset of the depressive disorder. In addition, a bidirectional association between depression and neurological disorder may be possible being that depressive syndromes may be considered as a risk factor for certain neurological disorders. As sustained by two recent meta-analysis, depressive syndromes, particularly major depressive disorder (MDD), are associated with a significantly increased risk of stroke[14,15]. On the other hand, lower rates of depression in equally impaired orthopedic patients suggest that PSD may even result from a stroke-specific neurobiological change and not only from a consequence of the psychological distress or the related impairments[16-18].

The second most common neurodegenerative disorder is represented by PD, with a prevalence of 1% of the elderly worldwide population. About 30% of PD patients show clinically significant depressive syndromes and, again, it appears to be also an increased risk for depressed patients to develop PD[19-23].

As far as regard MS, depressive syndromes are psychiatric most common disorders associated to the illness. Among individuals with MS, relative to the general population, lifetime prevalence rates are elevated for MDD (36%-54%), bipolar disorder (13%), anxiety disorders (35.7%), adjustment disorders (22%), and psychotic disorders (2%-3%). Suicide may be at least twice as common[1].

Many reports of depression and its correlation with numerous variables in clinical samples of people with MS have been published. The few population-based studies have reported a high prevalence of depression, despite using different methods of data collection. The lifetime risk of major depression in people with MS has been estimated to be as high as 50% compared to 10% to 15% in the general population[24,25].

In a recent cross-sectional, population-based study conducted in Stockholm county, the authors reported a prevalence rate of depression of 19% [Beck Depression Inventory (BDI) > 13] among patients suffering of MS. It’s interesting to note how depressive symptoms were associated with worse self-reported functioning, with poor memory function and with weak sense of coherence (SOC) (referring to ‘‘general resistance resources’’ - capacities that facilitate coping with stressors). Moreover, the authors suggested to incorporate depressive symptoms or mental health as a standard parameter for assessment and follow-up in clinical MS management[26].

Data from the United Kingdom MS Register, those obtained directly from MS patients, confirmed a high rate of anxiety and depression: over half of the respondents (54.1%) reported anxiety and 46.9% reported a variable level of depression[27]. From this registry data were recently examined about the positive relationships between physical disability, anxiety and depression[28].

Other reports confirmed the need to recognize and treat, having widely effective treatments, several emotional disorders which may worsen functioning and quality of life, decrease treatment adherence, and increase risk of suicide[1].

The prevalence of depressive disorders is higher in MS patients than patients with other chronic disease, suggesting a possible direct effect of the illness on the pathogenesis of the depressive syndromes in addition to the reactive disorder. Some evidences suggested that depression in MS is largely biologically mediated by some of the same processes involved in the immunopathogenesis of this neurologic disease. In particular, the increase in proinflammatory cytokines, the activation of the hypothalamic-pituitary-adrenal axis, and the reduction in neurotrophic factors. Notwithstanding, depression and mood disorders still remain under-diagnosed and under-treated in neurological patients claiming for a bio-psychosocial model be used[29-32].

Music therapy

In last decades, a growing body of evidence in the use of musical intervention in clinical setting have been seen, concerning singing, music listening, musical improvisation, and other musical activities, as long as more structured music therapy (MT) treatments. Given that music engages a variety of brain areas involved in emotion, motivation, cognition, and motor functions, musical interventions have been used to increase socialization and cognitive, emotional, and neuromotor functioning[33-38]. Although the debate on what the boundaries of MT is still going on, different approaches of musical intervention are actually available referring to three principal domains: relational approaches, rehabilitative approaches and music listening.

Relational approaches refer to psychological models and involve both active and receptive techniques[39,40]. The former consist of different musical activities such as free or structured musical improvisation by means of simple musical instruments, singing, songwriting etc. that allow patient and therapist to directly interact building a musical relationship[41]. In receptive approaches music imagery and music listening are used to induce psychological beneficial effects and even to evoke and process emotions and thoughts[40].

Rehabilitative approaches, such as Neurologic Music Therapy (NMT)[42] refer to neuroscientific models and use primarily the potential of musical stimuli to activate perception and production areas in the human brain, providing a series of therapeutic applications to sensory, cognitive, and motor dysfunctions resulting from neurological disorders. Using directive approach based on a series of exercises, NMT may be used, for example, to improve gait and movements in post-stroke and PD patients[43-47] and language in persons with aphasia[48,49].

On the other hand, simple music listening interventions don’t require neither a specifically trained therapist nor a direct therapeutic relationship with the patient being that beneficial effects are induced by the content of the musical stimuli and by the activity of listening itself. For these reasons, this practice is sometimes defined with the term “Music Medicine” rather than “MT”[41,50,51]. Notwithstanding, listening interventions seem to be quite common in clinical literature, usually based on self-selected or other-selected music proposed individually[52,53] or in group, as in the case of background music[54,55].

As far as regard neurological disorders, MT may promote functional recovery and also improve social and psychological outcomes such as socialization, motivation, mood, and depression[56]. Literature in this field shows that most of the musical interventions are currently used in clinical practice, being that the majority of the interventions are based on a combination of rehabilitative and relational techniques. Also music listening seems to be a common practice in neurological rehabilitation. Due to the possible side effects of pharmacological treatment of depressive syndromes following neurological disease, music and MT may represent a valid support in reducing depressive symptoms, improving mood and adherence to treatment while contributing to the functional recovery at the same time.

RESEARCH

PubMed and PsychInfo databases were considered for articles to include in the current narrative review. The research has been conducted by three independent reviewers using the following search terms: (“Music” OR “MT”) AND (name of pathology) AND (“Mood” OR “Depression”). Names of pathologies where used alone or in combination with “OR” Boolean operator and included: “Stroke”, “Parkinson”, “Dementia”, “Epilepsy”, “ALS”, “MS”, “Cerebral palsy”, “Neurological disease”, and “Acquired brain injury”.

We included only Randomized Controlled Trials (RCTs) or Clinical Controlled Trials (CCTs) studies in English language published in peer-reviewed journals between 1^st January 1997 and 31^st May 2014. Importantly, we considered only trials including outcomes concerning mood or depression where experimental conditions were clearly stated and consisted only or primarily of musical activities.

Assessments of methodological quality of selected studies have been provided using Jadad score[57]. Jadad scale is based on 7 items that evaluate three main characteristics of a clinical trial: the random assignment, the double-blinding of assessments, and the flow of participants. Scoring ranges from a minimum of 0 to a maximum of 5 points where a score of 3 indicates a good quality study. Being that 2 points on 5 are scored for double-blinding and none of the included studies had double-blinding assessment, the maximum possible score was 3. Even if it doesn’t take into account allocation concealment and has been criticized for placing too much emphasis on blinding[58], Jadad scale represents a simple, easy and common way to evaluate the methodological quality of a clinical trial with good validity and reliability[59]. Due to the heterogeneity of the outcomes, no meta-analysis was carried out.

DESCRIPTION OF SELECTED STUDIES

A total of 464 records resulted from the search of which 301 from PubMed and 163 from PsychInfo. Twenty-five articles that met the inclusion criteria have been found and were included in the current review. Most of the selected studies are related to dementia (44%) and stroke (36%) while others regard MS, ALS/motor neuron disease, PD, Chronic quadriplegia, and acquired brain dysfunctions (20%). Fourteen studies (56%) employed a relational approach including both active and receptive techniques, six studies (24%) adopted a rehabilitative approach, and five (20%) concerned music listening interventions. Activities were conducted by trained music therapists in the most part of the experimental interventions. As far as regard the methodological quality of included studies, our analysis showed that only nine on twenty-five (36%) of the included studies received a Jadad score of 3 and thus can be considered of good quality. Five studies (20%) had a Jadad score of 2, three studies (12%) a score 1, and eight studies (32%) were evaluated with a score of 0. Results of the methodological assessment pointed out a general poor rigor in research protocols.

Effects on dementia

Eleven studies assessed the effects of music and MT on dementia[60-70]. Eight studies employed a relational approach[60-61,63-65,68-70] based either on active or receptive techniques or a combination of both of them. Two studies concerned music listening interventions[62,67] and one study adopted a rehabilitative approach[66]. In most cases the results show a positive effect on mood, depression, and anxiety. Two studies revealed no significant effect of musical intervention[64,66] while in three studies both experimental and control group improved emotional and behavioral functioning in the same way[65,67,69]. Characteristics of the studies and main results have been summarized in Table ​Table11.

Effects on stroke

Nine studies assessed the effects of music or MT on post-stroke patients[71-79]. Four of them were based on a relational approach[71,72,76,77], three regarded music listening interventions[74,75,78], and two used a rehabilitative approach[73,79]. All studies show a positive effect of music or MT on mood in patients with Stroke. For a synthesis of studies and results please see Table ​Table22.

Effects on other neurological disorder

Five studies concerning other neurological disorders such as MS, ALS/motor neuron disease, PD, Chronic quadriplegia, and Acquired Brain dysfunctions, have been found[80-84]. Three studies concerned a rehabilitative approach[80,82,84] and two studies adopted a relational approach using an active technique[81] or both active and receptive techniques depending on what the therapist deemed appropriate in consultation with the patient[83]. All studies but one[83] reported positive effects of music and MT on outcomes as mood, depression, anxiety, and quality of life. Characteristics of the studies and main results have been summarized in Table ​Table33.

DISCUSSION

In the last few decades, the development of neuroscience demonstrated that the brain isn't a static structure only influenced by genetic determinants but it is a plastic organ that continuously reorganizes synaptic connections under the influence of inner and outer factors such as genetic programs, environmental stimulation, learning and expertise[85-87].

Neurological illnesses that provoke behavioral disturbances might originate from both endogenous and external causal factors thus determining, depending on the circumstances, a more “structural” or a more “environmental” etiology. The mutual interaction between these factors occurs in the brain and gives rise to a variety of psychiatric disorders that can be distributed upon a continuum, on one end of which are behavioral disturbances clearly linked to neuroanatomic and neurochemical alterations while on the opposite those more associated to the environment.

Synaptic functions and neuroanatomic structures are proper “organic” factors that determine those alterations that are usually treated by neuropsychiatry and biological psychiatry. Behavioral disorders resulting from these factors include psychiatric syndromes that are linked to alterations of the neural transmission caused by receptor’s abnormalities and by modifications of the synaptic concentrations of one or more neurotransmitters. Given that neurotransmitters regulate the neural impulse transmission processes into neurotransmitter systems, with a widespread projection in the brain, the whole emotional, motivational, and affective state of the person will be altered[88,89].

External causal factors related to the environment may promote and characterize those behavioral disorders that are commonly counted accordingly to a bio-psychosocial model and interfere with the cognitive and emotional state of the person thus inducing an important change in the quality of the inter-individual relationships. These disorders may be considered as a reaction to the physical disability and the psycho-social difficulties produced by the disease but also as an adjustment disorder if we consider the impact of the diagnosis on patient’s life, or the weight of a chronic illness and all the other factors that may affect patient’s quality of life[90-92].

Depressive syndromes in chronic neurological illness are common and disabling. Their etiology is complex and may be multifactorial. Good history taking and detailed examination of physical and mental state (including cognitive function) will usually reveal the diagnosis and the formulation.

Providing a correct diagnosis of an emotional disorder and starting an appropriate treatment may help physicians to increases in function and quality of life of their neurological patients[93].

The current review showed how MT and musical interventions can improve mood and psychological well-being in neurological patients. These clinical results are in accordance with the literature that highlights the effects that music listening and music making have on brain structures of emotion regulation[36], on various neurochemical systems[38], and on neural plasticity[94,95]. However, the strength of this review’s findings is limited due to a generally poor methodological quality of the studies and the restricted size of samples. Moreover, the heterogeneity of the outcomes prevented any meta-analysis. Notwithstanding, the analysis of the 25 RCTs or CCTs included in this work points out a positive effect of interventions with music on psychosocial outcomes such as mood, depression, and quality of life when compared to standard care or other treatments.

CONCLUSION

Music-based activities can represent a valid and without side effects intervention for reducing psychological and behavioral disturbances related to neurological disorders and also for promoting the functional recovery. Specifically, the most significant results of the music interventions on the psychological side can be identified in the aspects more closely related to mood, especially in the reduction of the depressive and anxiety's component, and in the improvement of the emotional expression, communication and interpersonal skills, self esteem and quality of life. As revealed in advance, the efficacy of music and MT interventions could be explained by different points of view. From the neurochemistry point of view we know that music can activate limbic and paralimbic structures, such as the amygdala, the hippocampus, the nucleus accumbens, etc. that function abnormally in patients with a high depressive component. At the psychological level music can engage several social functions, can increase communication and social cohesion and can promote empathetic relationships, especially in the active MT approaches. Finally, from the rehabilitative point of view, making music can involve and influence motor areas functioning and regulation. This effect appears to be connected to the pleasure and thereby can positively affect the mood and consequently the rehabilitative process[36-38].

In conclusion, a more methodological rigor and a clearer definition of music approaches are needed to improve the quality of MT research and to focus on the specific role of music-based interventions in psychological symptoms in the field of neurology.