Remedy in the Melody

After a physically and mentally draining day as a college student, I lay in my dorm bed with my phone speaker on my chest playing “Pursuit of Happiness” by Kid Cudi. As I listen to this song, I am transported back to my hometown of Hightstown, New Jersey, to my theater class, when I heard this song for the first time as I watched my classmate do a lip sync performance to it. Then, I am transported to driving on the highway at two a.m. on the way to the beach during the dead of winter with the windows down and the cold breeze blowing through my hair. This capacity of music to evoke strong memories in me made me wonder whether individuals with memory loss are also able to vividly relive past experiences through music.

Despite the progression of Alzheimer’s disease (AD) and its effects on my grandmother, she remained responsive to music. Up until her final days, though she would not respond when we talked to her, she would always tap her hand on the arm-rest of her wheelchair while listening to bhajans, Hindu devotional songs. I wondered whether she was also transported to different times of her life to re-experience old memories, such as raising her children during the Sri Lankan Civil War, despite her memory loss. Furthermore, if my grandmother and others who suffer from neurodegenerative diseases are unable to remember past experiences, can music help “rebirth” those memories? To understand this phenomenon, we must first understand memory formation and retention in the healthy brain and how emotions can influence these processes. This will allow us to discuss potential therapies to keep AD patients' brains engaged and alert through music.

How is Music Processed in the Brain?

The relationship between music and memory retention can be explored by understanding the pathway in which music is processed in the brain. First, the frequency, harmonics, duration, and volume of music are processed in the auditory cortex [1, 2]. Afterwards, a behavioral response, such as tearing up or foot-tapping, is elicited in the temporal lobe [2, 3]. This brain region is primarily responsible for interpreting sounds and is home to the hippocampus, which plays a crucial role in memory [4, 5]. Through analyzing electrical signals in the brain while participants listened to music, researchers found that listening to music specifically activated the cortical region in the temporal lobe and the supramarginal gyrus, which is partially responsible for some aspects of learning and language [3, 4].

According to this proposed pathway, my grandmother’s auditory cortex activated upon hearing the bhajans and generated behavioral responses, such as tapping her fingers to the rhythm of the music. The generation of behavioral responses in the temporal lobe suggests that the brain regions associated with memory may have been activated in response to music [3]. This suggests that despite her memory impairment, my grandmother might have been capable of recognizing the music she was listening to. By delving deeper into the relationship between music and memory, the question of why my grandmother still exhibited a behavioral response to music can be examined.

How do Emotions Connect Music and Memory

To determine music’s potential to enhance memory, it is crucial to grasp the distinct relationships between emotions and memory as well as music and emotions. Utilizing emotions as an intermediary allows us to examine whether music and memory are interrelated through the associative network theory of emotion and memory, created by cognitive psychologist G.H. Bower [6]. In 1981, Bower conducted a series of experiments where college students were induced into happy or sad moods by hypnotic suggestion and were then asked to recall a list of sixteen unrelated words. After ten minutes, they were asked to recall a different list of sixteen unrelated words, either in the same mood or an opposite mood than when recalling the first list. Results showed that students had better recall of the same-mood list and worse recall of the opposite-mood list. Bower thus concluded that participants exhibited mood-state-dependent memory when the emotional mood was a helpful feature in distinguishing words on either list [6]. Mood-state-dependent memory is the theory that a memory can be better recalled when a person is in the same emotional mood as when the memory was encoded [7]. Additionally, it was found that when the tone of a narrative agreed with the emotional mood of a reader, the saliency of the events in the narrative was increased [6]. A memory that is made prominent by one’s emotional response to music can be considered a salient memory [8]. These experiments allowed Bower to develop the semantic network theory which draws on the theory of mood-state dependent memory and suggests that emotions serve as memory units that can aid in the recall of events [6].

One study suggests that through mood congruency, music could evoke emotions which would improve memory recall [9]. Mood congruence is when the stimulus being encoded by an individual matches the mood state of the individual performing the encoding, which can be differentiated from mood-state-dependent memory in which the mood at the time of encoding matches the mood at the time of recall. Participants were asked to listen to fifteen different excerpts of music which were expected to elicit different emotions, and after each excerpt, were asked to look at four different pictures which either conveyed the same emotion elicited by the music (congruent pictures) or which conveyed a different emotion (incongruent pictures). Results showed that congruent pictures were more actively recalled than incongruent pictures which confirms that mood-congruence aids in memory recall of music-evoked emotions, suggesting that music can evoke emotions that are also associated with better or worse recall [9]. By mood congruency, bhajans are a happy or peaceful stimulus and—since my grandmother listened to them while happy or peaceful—she is more likely to remember these memories.

How the brain’s neural reward systems connect music and memory

According to Bower’s associative network theory, more salient memories are implied to be associated with strong emotions, such as pleasure, and consequently could be associated with stronger recall. Therefore, there could be a relevant correlation: the greater the enjoyment derived from a certain piece of music, the higher the likelihood of memory recall.

An analysis of past studies about the brain structures involved in music-evoked pleasure allows us to understand the connection between music-evoked pleasure and memory in the brain [10,11]. Researchers found that the brain’s dopaminergic mesolimbic reward network is important in motivation and reward behaviors in relation to music [10,11]. In this network, dopamine, which creates a feeling of reward, is released from the ventral tegmental area (VTA), which is critical for the development of behavioral reward [10].

Dopamine can modulate activity in the amygdala, a region of the brain that strongly influences memory formation in response to emotionally arousing experiences [12,13]. Additionally, it was found that the anterior hippocampus, the region of the brain which serves a major role in learning and memory, activated attachment-related emotions when promoted by music [11,14]. This suggests that while my grandmother was listening to pleasureful music such as bhajans, there was a dopamine release within her brain which specifically affected the amygdala and hippocampus influencing emotions and memory.

Researchers further studied the hypothesis that dopamine-dependent musical reward can improve memory [15]. To test this hypothesis, 29 female and male participants were asked to provide reward ratings for unfamiliar music excerpts. The participants were then

asked to retain this information under three different conditions: after inhibiting dopamine, stimulating dopamine, and a placebo. Ingesting a dopaminergic antagonist before the experiment blocks the dopamine receptor and prevents the dopaminergic mesolimbic reward system from working, therefore preventing the hippocampus and amygdala from functioning normally. On the other hand, ingesting a dopaminergic precursor encourages the formation of dopamine, and ingesting a placebo does not impact the function of the normal reward system. The results demonstrated that the greater the reward experienced while listening to the music, the better the memory recollection since the amygdala and hippocampus are activated through dopamine release [15]. During the Sri Lankan Civil War, my grandmother would often listen to bhajans as a way to feel protected by Hindu Gods. Since listening to this devotional music activated her reward circuitry, which in this case was mental comfort during the war, the memories associated with the music were strong.

Music: A potential therapy for AD

AD, a neurodegenerative disorder characterized by gradual memory loss, often involves an abnormal buildup of proteins, known as amyloid-beta and tau, which disrupt synapses (the connections between neurons) [16]. In patients with AD, the hippocampus is often affected first, causing individuals to be unable to store and recall short-term memory, and then eventually lose the ability to store long-term memory [16]. Through learning about the connections between memory and music, I wondered whether music therapies could help AD patients recall music-evoked autobiographical memories (MEAMS) and elicit strong emotions using state-dependent memory.

MEAMS are found to be preserved in patients with AD and occur as frequently as they do in healthy adults [17]. This finding is integral to finding ways to “rebirth” memories in patients with AD, since playing music that holds emotional significance can help them recall lost memories. In a 2018 study, 10 participants with AD and 10 healthy elderly patients listened to two familiar songs and reported their memories associated with the song. To determine the effectiveness of MEAMS over other emotion-evoking stimuli, MEAMS were compared to photograph-evoked autobiographical memories (PEAMS). Although PEAMS were found to be more frequent in healthy elderly than MEAMS, there was a significant decline in the presence of PEAMS in the elderly, whereas the frequency of MEAMS was the same between both groups [17].

One hypothesis explaining why MEAMS are preserved in the AD brain is that the continual engagement of the medial prefrontal cortex (mPFC), responsible for MEAM retrieval, preserves the function of that area of the brain [18]. Participants in a study were asked to listen to popular music clips and to view images of famous people in order to determine how mPFC damage affects an individual's ability to experience MEAMS. Results showed that those with mPFC damage experienced significantly fewer MEAMS than face-evoked memories. Since the mPFC is crucial in memory retention, therapies that include continuously reactivating the mPFC could help preserve memories in AD patients [18].

Not only does music help promote the retention of memory, music can also reduce biomarkers which are indicators of AD [19]. Telomere length (TL), telomerase activity (TA), and plasma amyloid-beta levels (Aβ) were found to be predictors of cognitive decline and dementia which are common symptoms of AD [19]. Telomeres are DNA proteins at the end of chromosomes that shorten with age and disease, such as AD, as a result of cell death [20]. In a 2018 study, the effects of music listening on the blood biomarkers of dementia patients were studied by administering 12 minutes of the patient’s choice of six classical music compositions a day [19]. After three months, TL and TA were measured, and after three and six months, cognition, stress, sleep, and mood were measured. Results showed that increases in TA and TL when listening to music were associated with improvements in memory and cognitive function [19]. Additionally, after listening to music, Aβ levels in the blood rose resulting in lower Aβ levels in the brain which contribute to AD. This change Aβ

levels improved cognitive function, mood, and sleep [19]. If listening to music can help to reduce the biomarkers of AD, then it can help with slowing down the impacts of the disease.

Potential Role of Music in Neurogenesis

Although improvements in memory through reducing biomarkers and MEAMs help to temporarily relieve memory loss and slow down further neurodegeneration, there still remains the question of whether there is a possibility for music to play a role in neurogenesis, the formation of new neurons, in the adult brain [21].

Neurogenesis is a fascinating theory since, unlike other tissues in the body, neurons in the central nervous system, with the exception of the hippocampus, do not regenerate after dying due to age [22]. However, music-evoked memories were found to activate the anterior hippocampal formation, which could be suggestive of potential neurogenesis in AD patients [23]. If music-evoked neurogenesis occurred in the hippocampus this could help decelerate hippocampal atrophy and could help recover loss of hippocampal volume, which is the area first impacted by AD [23].

In 2008, researchers proposed that listening to music could facilitate the neurogenesis, regeneration, and repair of neurons through the secretion of steroid hormones leading to cerebral plasticity [24]. Neuroplasticity includes the structural changes and reorganization in the brain in response to a stimulus and the formation of new synapses [23].

In this experiment, participants listened to preferred calming music and non-preferred music [24]. Their saliva was collected to study the changes in testosterone, estrogen, and cortisol levels before and after the experiment was conducted. Testosterone and estrogen are both associated with the expression, regeneration, repair, and protection of nerve cells and were found to regulate levels of AD biomarker Aβ [24, 25]. Additionally, estrogen is associated with brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which are factors that have been linked to neurogenesis [25]. Cortisol is a steroid hormone that is responsible for mediating stress response, metabolism, inflammatory response, and immune function. Results showed that in males, testosterone and estradiol levels decreased after listening to both types of music. However, for females, testosterone and estradiol levels increased when listening to calming music but decreased when listening to music they did not like. In women who suffer from AD specifically, it is found that lower levels of estrogen contribute to the accumulation of amyloid-beta which is a predictor of AD, therefore, listening to music helps to regulate estrogen levels and the accumulation of amyloid-beta. The increases and decreases in these hormone levels exhibit signs of neuroplasticity, which can be linked to neurogenesis, suggesting that listening to music may be able to regenerate nerve cells [24]. Although this research on neurogenesis in relation to AD is promising, neurogenesis has predominantly been studied in adult rodent hippocampus and has yet to be studied more in humans [26].

Music currently used as an intervention in hospitals

Given how scientific evidence has pointed to music having the potential to improve cognitive functioning in patients with neurodegenerative disease, it is beneficial to note how the field of music therapy operates in hospitals currently, especially in regard to patients with neurological dysfunction.

Music has already been used as a form of therapy intervention in hospitals [27]. For example, it has been used in treating patients experiencing delirium, a potential symptom of AD. Delirium, a syndrome of acute brain failure typically occurring in the elderly, results from an underlying medical condition causing alteration of attention, consciousness, and cognition. Hospitals have found that listening to music helps decrease heart rate, blood pressure, and cortisol levels in delirium patients in the intensive care unit (ICU). A clinical study was conducted to examine two music interventions used on delirium patients. ICU delirium patients listened to either a personalized music playlist based on personal preference, non-personalized slow-tempo music (STM), or audiobooks for attention control. 80% of participants reported that they enjoyed these sessions and listening to STM showed decreases in patient anxiety and pain. However, there was a significant increase in blood pressure and heart rate in the treated patients. This suggests that maybe listening to music didn’t help treat the delirious patient’s physiological discomfort, but was beneficial through another pathway [27]. Further studies are required to extensively detail the mechanisms by which music helps to improve delirium and AD in general.

A study examined music as a method of evaluating the daily symptoms and improving the cognition and mental well-being of AD patients [28]. A group of 298 AD patients were divided into three groups: a music therapy group that sang or listened to songs twice daily for three months, a lyric reading group which read lyrics of songs without the melody twice daily for three months, and a control group that received no interventions. After the three-month period and a six-month period, cognitive function, mental state, and verbal assessments were conducted. It was found that music therapy led to higher scores in verbal fluency in mild AD patients, and decreased psychiatric symptoms in severe AD patients as compared to the other groups [28]. Additional studies examining how music therapy affects patients with mild, moderate, and severe AD differently are needed to confirm these findings.

Though my grandmother was never able to experience the benefits of music therapy, casually listening to bhajans at home was able to relieve some of her psychological and physical pain. Through understanding how our ability to emotionally connect with music influences our memory retention and recall, we are able to understand the importance of music in not only preserving memory in healthy individuals but also as a therapy for those like my grandmother who suffer from neurodegenerative disorders like AD. Although further studies are required to confirm the links between music and neurogenesis, the promising nature of this research could eventually help find a cure for AD and other forms of dementia. I will never have an answer to whether or not my grandmother was able to transport herself back in time to re-experience old memories through music the same way I am able to. However, research on music and memory in relation to AD brings us closer to a solution of how we can use the power of music to alleviate the pain of those suffering from neurodegeneration and allows us to further explore whether music can truly “rebirth” lost memories.