Soft-Wired: Brain Plasticity and Therapeutic Applications

Background

“Neuroplasticity” refers to the “functional and structural alterations in the brain enabling adaptation to the environment, learning, memory, as well as rehabilitation after brain injury” (Gulyaeva, 2017, p. 237). The brain’s ability to adapt enables one to cultivate sensory-cognitive functions (Merzenich, 2013), substitute senses (Rutkin, 2013), rehabilitate damaged neurological functions (M. Thaut & Hoemberg, 2016), and advance cognitive capacity (Merzenich et al., 2013). Plastic change in the brain results in measurable modifications in the brain’s neural structures, and can be facilitated to achieve specific goals by a professional privy to the underlying mechanisms that mediate it (Cramer et al., 2011; Doidge, 2007; Hawkins, 2021; Merzenich et al., 2013; Merzenich, 2013; Merzenich et al., 2014; Taub, 2015). Various scientists have alluded to this concept of plasticity throughout the last several centuries (Doidge, 2007; Gulyaeva, 2017). In fact, the notion of nervous system plasticity was evident in ancient Greek philosophy. Music and gymnastics are often mentioned as integral components of basic education in The Republic, the legendary book in which Socrates argued that one can train their mind in the same way gymnasts train their body (Plato, 380 BC).

Up until a few decades ago, the notion of post-critical period brain plasticity was largely derided within the neuroscience community. Most experts believed that the brain was “fixed” in structure and function, a theory known as “locationism”. The locationist theory asserted that the brain is only plastic within the “critical period”, a developmental window of substantial neural organization in the beginning of one’s life (Hübener & Bonhoeffer, 2014), which has been observed in both animal (Hubel & Wiesel, 1964) and human (Kim et al., 1997) brains. This paradigm inculcated a view of the post-critical period nervous system as ‘hardwired’ and unable to adapt to training or compensate for neurological injury. For years, medical students were taught that there are specific centers in the brain that are responsible for specific functions, and damage to a given center will result in permanent disability.

Yet, this locationsist notion is not entirely untrue, as there are numerous areas of the brain specifically devoted to specific aspects of processing information (Burton et al., 2005; Peterson et al., 2022; Vanderah & Gould, 2020). For example, both the Wernicke’s and Broca’s areas are well known to be chiefly responsible for the processing of speech perception (Javed et al., 2022) and production (Stinnett et al., 2022). Damage to these areas will surely result in linguistic dysfunctions (Fridriksson et al., 2015).

However, the amelioration of the debilitating post-injury effects on these processing centers has been well documented (Doidge, 2007). There is also a significant body of literature regarding the use of evidence-based clinical interventions to facilitate such rehabilitations for both congenital and acquired disabilities (Aldridge, 2005a; Baker & Tamplin, 2006; O’Sullivan et al., 2019; M. Thaut & Hoemberg, 2016). Here, we stand at the forefront of a new frontier in the study of neuroscience, education, and medicine.

Indications of Brain Plasticity

A series of brilliant studies have examined brain plasticity in an attempt to understand the underlying mechanisms of the phenomenon. In the early 20th century, some neurologists were exploring how the artificial stimulation of neurons might affect a subject. One noteworthy individual involved in this pursuit was American-Canadian neurosurgeon Dr. Wilder Penfield, who often operated on epilepsy patients. In order to identify which brain parts could be removed, Penfield mapped out the cortical brain using electrodes (Penfield & Rasmussen, 1950). These examinations rendered the proverbial Homunculus Man, a representation of the somatosensory neurons within the cerebral cortex in which the size of each body part is proportionate to the amount of neurons involved in feeling touched in that area (Catani, 2017). A significant finding here was that the somatosensory cortex is topographically arranged, meaning that body parts adjacent to each other have corresponding sensory neurons that are likewise adjacent to each other in the brain’s sensory maps.

Two studies worth unburying involved stimulating various neurons in the exposed brains of patients and observing the corresponding response (Brown & Sherrington, 1912; Lashley, 1929).They found that stimulating a given motor neuron with electrodes resulted in an involuntary movement, and likewise with tactile stimulation of sensory neurons. One of the baffling observations they made was that the motor neurons triggering a given movement would sometimes be different when the researchers stimulated it again sometime later. This suggested that the cortical maps are dynamic; an astonishing result that scientists could not make sense of at the time.

Dr. Michael Merzenich is a neuroscientists and professor emeritus at University of California, San Francisco. He is highly regarded among his colleagues as the world’s leading researcher on brain plasticity. Upon digging through these forgotten studies, he decided to replicate the procedure with microelectrodes, a tool that allows far greater precision than those used decades before. He prepared for these studies with the painstaking process of mapping out the sensory cortex in monkey subjects. This process involved inserting a microelectrode onto a given neuron, then tapping various body parts until the electrode received an impulse. This indicated that the corresponding neuron was responsible for feeling “touched” in that part of the body. He repeated this process until the entire map of a given body part was identified, then conducted a series of experiments to observe how these maps might change or adapt to various circumstances. One of these studies examined the somatosensory neurons in the brain of an adult monkey (Merzenich et al., 1984). They mapped out the sensory neurons responsible for the touch sense in the entire hand, and proceeded to amputated the middle finger. With absent stimuli from the amputated finger, the somatosensory neurons responsible for somatosensory stimulation in that region in the hand went dark. In response, the sensory neurons responsible for that region of the hand were reallocated to receive stimulation from the adjacent fingers, making use of this suddenly unoccupied neural real estate. This evidence of sensory neuron reallocation suggests that the post-critical period brain is capable of adapting to novel experiences.

Another study involved the sensory nerves in the hand of an adult monkey (Merzenich et al., 1983). Monkeys, like humans, share the same structure of sensory nerves to the hand. The three major nerves include the radial, median, and ulnar nerves (Rapp & Soos, 2022). In this study, Merzenich severed the median nerve to observe how the brain map responsible for that area of the hand would respond. Upon remapping two months later, he found that the brain map that had previously served the median nerve showed no activity when touched. This was expected, although there was another result he did not anticipate. “As he stroked the outside of the monkey’s hand - the areas that send their signals through the radial and ulnar nerves - the median nerve map lit up! The brain maps for the radial and ulnar nerves had almost doubled in size and invaded what used to be the median nerve map. And these new maps were topographical” (Doidge, 2007, p. 59). These findings suggest that if a section of a sensory map was deprived of input, the unused portion would be reallocated to process stimuli from other functioning nerves, demonstrating the universal neuroplastic principle of “use it or lose it”. Another interesting observation Merzenich made was that, even though animals of a particular species may have similar cortical maps, they were never identical. Micro-mapping the brain with smaller electrodes allowed him to see differences that Penfield and others could not.

This phenomenon has also been observed in human subjects. Using Transcranial Magnetic Stimulation, neuroscientist Alvaro Pascual-Leone mapped the motor cortex in people learning to read braille (Pascual-Leone et al., 1999). What he found was that “the maps representing their ‘Braille reading fingers’ were larger than the maps for their other fingers and also those for the index fingers of non-Braille readers. Pascual-Leone also found that the motor maps increased in size as the subjects increased the number of words per minute they could read” (Doidge, 2007, p. 198).

Ultimately, plasticity is a perpetual process, and it is the nature of nervous systems to undergo constant change. “Plasticity doesn’t require the provocation of cut nerves or amputations. Plasticity is a normal phenomenon, and brain maps are constantly changing” (Doidge, 2007, p. 61).

The Neurochemical Mechanics of Post-Critical Period Brain Plasticity

Neuroscientists now have a basic understanding of how brain plasticity works in the post-critical period brain. During the critical period, any experience makes an imprint on the brain (Berardi et al., 2000). In the adult brain, plasticity is regulated through behavioral means (Merzenich et al., 2013). These behavioral components include arousal levels, motivation, conscious focus, and rest.

Some of the modulatory neurochemicals responsible for plastic change are acetylcholine, norepinephrine (noradrenaline), and dopamine (Merzenich et al., 2014). Brain plasticity can be simply understood as a 2-step process; priming synaptic changes during training and consolidation during rest and sleep. The above-mentioned chemicals play a significant role in the first step. However, research shows that sustainable plastic change can only occur with adequate sleep and non-sleep-deep-rest (NSDR) (Eichenlaub et al., 2020; Frank et al., 2001; Immink, 2016; Huberman, 2021; Wilson & McNaughton, 1994).

Step One: Priming and Pruning Synaptic Connections

The nucleus basalis (NB) is a structure deep within the brain that contains a large population of cholinergic neurons which project to a wide range of cortical and subcortical regions of the brain (Kilgard & Merzenich, 1998). Under states of acute focus, the NB is engaged by any neural activity generated in a closely attended behavior. Once engaged, “a plasticity-enabling epoch is open for several minutes” (Merzenich et al., 2013, p. 146), where the corresponding neurons are susceptible to synaptic reconfiguration. In other words, conscious awareness and focus are crucial for learning.

A second set of processes are mediated by the neuromodulator norepinephrine (NE). The locus coeruleus (LC), Latin for “blue spot”, is a pontine nucleus that produces a large portion of the brain’s NE (Schmidt et al., 2020). The LC also projects throughout several cortical and subcortical structures and plays a significant role in the plastic process. NE, functioning as a both a stress hormone and modulatory neurotransmitter, will mediate a second set of processes by “amplify[ing] the activity generated by any unexpected event or by any closely attended behavior” (Merzenich et al., 2013, p. 146). A noteworthy phenomenon observed in several studies (Aston-Jones & Cohen, 2005; Sara, 2009; Sara & Bouret, 2012) is that the effects of NE are “rapidly attenuated if that input is nonvariant” (Merzenich et al., 2013, p. 146). In other words, practice or training regiments must be varied in order to make a lasting impression on the neurons involved in the activity at hand. Mindless monotony will not result in sustainable change in the brain.

What we know about the functional nature of NE indicates that adequate levels of arousal and focus are necessary in the process of facilitating plastic change (learning) in the adult brain. This process, which can be described neurochemically as stress, is essential to the learning process. A helpful paradigm shift here is from a common perception of stress. Understanding stress as an integral neurochemical phenomenon might provide a view of the experience as helpful and necessary in appropriate levels to facilitate learning. This can be described as ‘eustress’ as opposed to distress or traumatic stress.

Lastly, a third set of processes are mediated by the modulatory neurotransmitter dopamine (DP). DP is produced by a midbrain nucleus called the substantia nigra (SN), which plays a critical role in motivation, reward, and movement (Sonne et al., 2022). DP modulates a set of processes by selectively controlling the plasticity for activity that had occurred prior to a rewarding event. This modulatory process also engages after an event that the brain judges to be positive (Merzenich et al., 2013). Dopamine serves to enable change for inputs that contribute to a given success, and weakens competitive activities that are unrelated to that success. A significant consideration here is that the neuromodulatory effect dopamine can have on plasticity can be highly contextual, as the plasticity enabling process largely engages in events that an individual deems appropriate or desirable. Dopamine is involved in feelings of satisfaction in a completed task, but also highly involved in motivation and goal seeking (Lieberman & Long, 2018). That is why DP, widely regarded as the ‘pleasure molecule’, can be more aptly characterized as a modulatory ‘motivation molecule’.

In review, acetylcholine acts as a ‘highlighter’ for neurons engaged in a given task, and triggers the cultivation of synaptic connections according to the task’s demands. Norepinephrine, acting as both a stress hormone and neuromodulator, supports the process by selectively amplifying inputs involved in a task. This process is further supported by dopamine, which serves to strengthen circuits related to a perceived success as well as provide motivation to achieve a given goal.

Step Two: Consolidation During Rest and Sleep

Recent studies conducted with human subjects have elucidated the significance of rest and sleep for the consolidation of memories and learned behavior. It is important to note that neuroplasticity is a process rather than an event. One study showed that synaptic renovations induced throughout the learning process are consolidated under periods of rest and deep sleep, as the experimental group who received adequate sleep achieved far greater retention of information compared to the control group who were deprived of sleep (Frank et al., 2001). Another study indicates that a brief moment of NSDR can help to strengthen and solidify the synaptic connections made during a period of learning (Eichenlaub et al., 2020). NSDR can come in many forms, including meditation and yoga. It might be accurate to propose that any activity that enables the brain to relax and suspend closely attended processing will do the trick. When one allows the brain to rest, it will “rehearse” the actions learned through a learning session in greater speed and succession during sleep and NSDR, a process Huberman calls “neural repetitions”.

The Neuromodulatory Machinery of the Brain is Also Plastic

Another significant consideration is that the neuromodulatory machinery involved in learning is, itself, plastic. There are indications that learning processes can be upregulated or downregulated through intensive training or pharmacological intervention (Merzenich et al., 2013). Indications of this are found in a study that utilized pharmaceutical drugs to severely dysregulate the acetylcholine-based processes that mediate plasticity in infant rats, resulting in abnormal development in the subjects. Through neuroscience-informed training, the researchers were able to remediate this confounded machinery and bring normal levels of dopamine, acetylcholine, norepinephrine, and serotonin (Zhou et al., 2011). Another study suggests that an artificial critical period could be implemented by stimulating the nucleus basalis with implanted micro-electrodes (Kilgard & Merzenich, 1998). This bidirectional neurochemical perspective of brain plasticity is helpful in understanding the process of learning in adult brains.

Neuronal Ensembles

A sound theory in brain functioning first proposed by behavioral psychologist Carl Lashley asserts that neurons typically function as large groups, or “neural assemblies”, to process information or execute a given task (Doidge, 2016). This would mean that “learned skills and behavior are encoded not ‘in’ specific neurons, or even ‘in’ the connections between neurons, but ‘in’ the cumulative electrical wave patterns that are the result of neurons firing together” (Doidge, 2016, p. 107). When we learn or perform a skill, we are activating a distinct combination of neurons to perform the task at hand. Insights regarding the neurochemical mechanics of plasticity offered by a plethora of research teams indicate that the learning process involves recruiting and pruning neural assemblies to enable one to execute a given task with the greatest possible precision and efficiency.

Furthermore, the above-mentioned sleep studies show that the neuronal networks curated through the training period are firing in increased rates during sleep / NSDR to consolidate the information. As shown in the Eichenlaub study, even a 10-second rest inserted into a practice / learning / study session will result in these accelerated neural repetitions, which in turn help to reinforce the neural activations one is striving to integrate. An understanding of this process potentially enables one to manipulate this neurochemical machinery to induce or inhibit neuroplastic change, a natural process one might exploit to facilitate learning with greater precision and potential capacity.

Plasticity Processes are Bidirectional

Neuroplastic change follows Hebbian principles: “representations of inputs and actions are competitively sorted on the basis of the temporal distributions of inputs” (Merzenich et al., 2013, p. 148). In other words, neurons that fire together wire together. According to these principles, “it is just as easy to degrade the brains processing abilities as it is to strengthen or refine it” (Merzenich et al., 2013, p. 148). When conducting neuroplastic therapy, whether as a clinical intervention or in education, it is important to be aware of these principles so as to assure the changes driven are in positive, strengthening, recovering, or renormalizing directions.

As mentioned earlier, the actions of dopamine are largely mediated by what the brain evaluates as a ‘positive’ achievement. By this principle, one might smoke a cigarette which sets a range of neurochemical dynamics in motion (Jiloha, 2010). Upon the intake of nicotine, there is a substantial release of neurotransmitters that induce feelings of pleasure and mood modulation. As far as the brain is concerned, this is a good thing. The action is encoded with the message “yes, do more of that!”, and is reinforced with every repeated action. The neurochemical process by which one develops an addiction to a substance is well understood, and results in measurable chemical modifications in the brain (Gardner, 2011). The brain may perceive the action as a positive event, and develop plastic changes toward habituation. However, it is clear that consistent smoking can be detrimental to one’s health in a myriad of ways (Campbell, 1999).

Another interesting maladaptive neuroplastic change is in the form of a movement disorder called focal hand dystonia (FHD), a condition that affects 1 in 2500 people (Torres-Russotto & Perlmutter, 2008). FHD is characterized as “excessive muscle contractions that can produce involuntary movements and abnormal postures” (Torres-Russotto & Perlmutter, 2008, p. 1). The pathophysiology of FHD is not well understood. However, there is evidence of the disorder having neuroanatomical etiologies. Structural and functional abnormalities of the basal ganglia and the various related pathways have been observed in individuals with FHD (Torres-Russotto & Perlmutter, 2008). The basal ganglia is a group of subcortical nuclei that mediate motor movement (Lanciego et al., 2012), the dysfunction of which plays a significant role in the development of neurodegenerative movement disorders such as Parkinson’s Disease (Lew, 2007).

One theory on the pathophysiology of FHD asserts that the disorder is a result of somato-sensory-motor dedifferentiation (Recanzone et al., 1992). To put it simply, the brain maps responsible for receiving information and conducting movements have become mis-wired and noisy, resulting in involuntary movements and general motor dysfunctions. In an attempt to explore this hypothesis, a team of physical therapists and neuroscientists conducted a study that aimed to artificially induce FHD in two owl monkeys (Byl et al., 1997). After a 20-week training protocol, the sensory and motor brain maps for the subjects’ hands were significantly more deteriorated and dedifferentiated compared to the control group that did not receive the training. The conclusion they drew was that highly articulated, nonvariant, and repetitive hand movements can lead to dramatic structural changes in the sensory-motor maps in the brain. Ultimately, this research suggests that one could elect to train their hands to make the sophisticated movements necessary to perform a Bach suite just as easily as one can train the hand to become a useless claw (Merzenich, 2013).

Conclusion

In conclusion, one can think of these neural assemblies as the formation of a musical orchestra. Each member has a specific role in the process to achieve a given goal. If a member is sick and unable to attend the concert, this does not necessarily mean that the entire band is unable to perform. However, it will mean that a component will be missing. The band leader can either allow the show to go on without this member, or recruit another musician to fill in the position. This, in neurological terms, might be described as neural compensation or substitution. If a patient experiencing traumatic brain injury has sustained damage to a certain brain region, they might compensate by recruiting alternate pathways, just as one might navigate a circuitous route in response to a highway closure. With repeated travel along this alternate route, it might develop from a country backroad to a super-highway. (Doidge, 2016).

Another keen analogy provided by Merzenich in his book ‘Soft-wired’ is the concept of neural coordination. One can imagine the brain as a stadium full of vivacious sports fans. If each member in attendance is clapping and yelling to their own rhythm, this would result in a tremendously discordant noise. If two members began clapping in unison, steadily recruiting others to contribute to the rhythm in an orderly fashion, the entire stadium might eventually transform the cacophonous calamity into a neatly coordinated song (Merzenich, 2013). The concept of a ‘noisy brain’ is an important consideration in conducting neuroplastic therapy and education, as optimal processing or execution of a task requires harmonious neural coordination. This insight is helpful in understanding the process of facilitating plastic change in clinical intervention and learning, the work of a myriad brilliant clinicians called “neuroplasticians”.

The Work of Neuroplasticians: Evidence-Based Neuroplastic Therapy

Stages of Neuroplastic Healing

In an effort to provide a paradigm for the facilitation of neuroplastic healing, Dr. Norman Doidge proposes a set of successive principles. Some patients need only a select few stages to heal, whereas some will need to pass through all of them.

Correction of general cellular functions of the neurons and glia

This stage focuses on the general health of neurons, and the functions they have in common with other cells. In many cases, the brain can become mis-wired because of a disturbance from external sources, including infection, toxins, pesticides, a drug, or food sensitivity. They might also be undersupplied with resources, such as certain minerals. These general issues are best ameliorated before beginning the stages that follow. Some practitioners have observed progress in patients experiencing attention deficit disorder, bipolar disorder, and depression by simply eliminating certain foods from their diet such as sugar and grains (Smith, 2015).

A consideration of the glial cells is typically warranted, as the brain does not contain a lymphatic system. Instead, the brain is protected from invading organisms by microglial cells, one of the unique ways the brain will protect and heal itself. The glia also serve to dispose of waste created by the brain (Lenz & Nelson, 2018). The general health of neurons is typically an important initial consideration when conducting neuroplastic therapy.

Neurostimulation

There is strong evidence supporting the use of a wide range of modalities to facilitate plastic change, including light (Dobbs & Cremer, 1975), sound (Geffner & Ross-Swain, 2013), electricity (Doidge, 2016, Chapter 7), and movement (Feldenkrais, 2005, 2010, 2019). Even conscious thought has shown to stimulate the brain and generate plastic changes (Yue & Cole, 1992). All of these modalities provide neurostimulation in part by reviving dormant circuits and leads to an improved ability of a noisy brain to regulate and modulate itself and achieve homeostasis. An example of neurostimulation in the form of thought is provided by the eccentric pain specialist Dr. Michael Moskowitz, who created mental exercises to help placate chronic pain experienced by patients from injuries long after they have healed (Moskowitz, 2008). “Every day thought, especially when used systematically, is a potent way to stimulate neurons.” (Doidge, 2016, p. 109). Neurostimulation, whether from an internal or external source, is an effective way of facilitating brain health.

Neuromodulation

Neuromodulation is the practice of restoring the excitation and inhibition of neural networks to quiet the noisy brain through various modalities. One way neuromodulation works is through by resetting the brain’s level of arousal by acting on certain systems. One of these systems is the reticular activating system (RAS), which is a structure in the brain stem that regulates arousal levels (Arguinchona & Tadi, 2021). Doidge explores the practice of resetting this structure through the modalities of light, sound, electricity, and vibration. Acting on the RAS can help patients to begin sleeping more deeply and wake up more energized and restored.

Another system one can modulate is the autonomic nervous system (ANS). The ANS is a plethora of ancient circuits that regulate physiological activity, as well as mediate survival and rest mechanisms. The branch that mediates the survival mechanism is the sympathetic nervous system (SNS), a branch of the ANS. The SNS, known for activating he fight-or-flight response, serves to mobilize the organism to fight or flee from a threat. This system is a necessary component for survival, although the physiologic state it induces is not conducive to learning and healing. Learning to engage and disengage this system is a form of neuromodulation.

Another branch of the ANS is the parasympathetic nervous system (PNS), which is known as the rest-digest-repair- system. This branch turns off the SNS to mediate a calm state so one can think and reflect as well as triggering the physiological conditions necessary for health and vitality. One physiological activity associated with parasympathetic activation is the recharging of mitochondrial cells, which are the source of energy within cell (Brand et al., 2013). Another significant finding regarding the activation of the PNS is the improvement of signal-to-noise ratio in brain circuits (Hasselmo et al., 1997). A common objective in neuroplastic neuromodulatory therapy is the practice of activating the PSN to relax the patient and prepare them for physiological health and growth (Doidge, 2016).

A beautiful theory of the ANS is provided by Dr. Stephen Porges (Porges, 2007). Porges considers the ANS as a phylogenetic hierarchy with multiple structures and functions developed throughout the evolutionary development of the human body. This theory suggests that throughout each evolutionary development of the nervous system, new circuits have grown to mediate the preceding structures.

A significant insight the PVT provides is within what is known as the “vagal paradox”, which states that the vagus (Latin for “wanderer”) nerve – the primary nerve of the PNS - is responsible for rest and restoration as well as causing maladaptive survival mechanisms such as freezing, defecation, and even death. The explanation for this is in the phylogenetic hierarchies of the system. The subdiaphragmatic nerves of the PNS are much older in evolutionary terms, and mediate the latter maladaptive functions. The phylogenetically younger circuits reside within the supradiaphragmatic regions of the body and mediate the more well-known functions of rest and restoration. The supradiaphragmatic vagus also innervates the throat and facial afferent and efferent nerves to mediate social engagement, giving this section of the PNS the name “social engagement system”. This section of the PNS developed when human beings adapted to rely on social cohesion as a more fundamental aspect of human behavior and functionality, as working together allows a more pragmatic way of living to ensure survival. This is why the theory is called “polyvagal”, as the vagus nerve innervates a myriad of locations within the body and has multiple functions (Porges, 2014). The PVT provides a brilliant framework with which one can understand and facilitate autonomic activity.

Neurorelaxation

Once the ANS is in balance, the patient can accumulate the energy necessary to manage their recovery. An interesting recent finding regarding neurorelaxation is that glial cells in the brain will open channels to discharge various neurophysiological detritus from the brain, including toxins and waste products (Xie et al., 2013). During sleep, these channels can be 10-times more active, thereby reducing toxicity in the brain.

Neurodifferentiation and Learning

Once these fundamental aspects of brain health and functionality are mediated, one can effectively facilitate learning or therapy. The process of neurodifferentiation can be described as making fine distinctions within various neural networks. In the context of therapy, neurodifferentiation can be helpful in rehabilitating neurological disfunctions in patients with various conditions. For individuals with cerebral palsy, there is often a dysfunction in somatosensory maps and motor pathways (Vitrikas et al., 2020). One can remediate this issue by helping the individual to differentiate these maps and pathways so they can operate themselves in a more functional manner.

In the context of learning, a musician will learn to differentiate the brain maps responsible for processing auditory stimuli. This is done through the practice of ‘ear training’, although a more accurate description for this practice is ‘brain training’, as we are developing the sensory maps in the brain. Ear training helps the individual to make finer distinctions in auditory stimuli processing so one can more clearly distinguish and identify various aspects of the sound, including note intervals, chord qualities, and timbrel character.

The concept of neurodifferentiation can be applied to a myriad of aspects of the nervous system, and is essentially ‘mapping out’ neural real estate so one can operate the given function with greater functionality and sophistication (Doidge, 2016).

Cheryl’s Accelerometer

The sense of balance is something that is easy to forget about until it goes awry. Following a post-surgical infection, Cheryl’s doctor prescribed Gentamicin - an antibiotic drug known to poison the inner ear and cause balance issues, tinnitus, and hearing loss if used too long (Modi et al., 1998). She used it too long, and lost 99% of her vestibular function. The result was extreme vertigo, where she was constantly pushed over by invisible forces. Even when she fell down, the torment would continue with a feeling that resembled a hole opening in the ground to perpetually consume her. Upon revisiting the doctor, she was told that the condition is permanent and will disable her for the rest of her life.

She then visited Paul Bach-y-Rita, a practitioner known for his divergent hypotheses and remarkably bizarre yet prescient inventions. By that time, Bach-y-Rita had been exploring neuroplastic therapy for decades, despite the virulent resistance he received from his colleagues (Rutkin, 2013).

He equipped Cheryl with an accelerometer, a sensory augmentation biofeedback machine. This device, closely resembling a construction hat, mimics vestibular function with sensors that detect motion in space. The data collected from the device is transmitted to a computer so a practitioner can monitor the activity, as well as a small chip the thickness of a piece of gum. Embedded within the chip are 144 electrodes that Cheryl places on her tongue. Whenever Cheryl’s hat detects her moving, it sends electrical impulses to her tongue to indicate the motion. This device helps Cheryl to regain her vestibular function through ‘sensory substitution’, a neuroplastic therapy technique of replacing one sense with another. Devoid of a functional vestibular apparatus, her brain is now receiving the information through tactile stimulation. While wearing the hat, she is promptly able to adapt to the new orientation and regain her balance. With a touch of time, she forgets that the information is coming from her tongue and can read her body’s position in space. Once the device is withdrawn, she is returned to her previous state of vestibular chaos.

Eventually, however, something incredible happens. After a few sessions, she experiences a residual effect of vestibular functionality after retiring the device. This effect is brief at first, but then begins to grow and compound. With consistent sessions, or “trainings”, the residual effects become longer until her vestibular functions are entirely recovered. Cheryl is now completely healed following this elegantly brilliant intervention (Danilov et al., 2007).

The Cochlear Implant

Hearing loss is a disabling condition that affects approximately 5% of the global population (World Health Organization, 2022). Throughout the last couple decades, several research teams have designed prototypes intended to ameliorate this issue. One of the companies, Advanced Bionics, created a cochlear implant through the research of Merzenich and his team. The cochlear implant is a “surgically implanted device that electrically excites the auditory nerve via a long thread-like array of stimulating electrodes” (Merzenich, 2013, p. 23). This device bypasses the cochlea to provide stimulation directly to the auditory nerve, essentially acting as an artificial cochlea. It consists of several pieces of technology including a microphone, a sound processor, and an electrode array that connects to the auditory nerve.

The greatest predicament in the application of this device was the challenge of supplying the auditory nerve with the sensory intricacies that matched that of the natural cochlea. The electrode array provided falls far short of providing such sophistications, being akin to someone attempting to play a complex classical piece with their fists. As a result, when patients first heard someone speaking after their cochlear implant, the voices were noisy and unintelligible.

One of the first patients who participated in the pilot study was named Earl, a 60-year-old man who had lost his hearing in the last few years. Upon assessing his auditory abilities, they found that he was unable to distinguish the words spoken to him. The word “car” would sound like “kera”, “box” like “brruh”, “damp” like “aahema”.

They decided to try a different technique. Earl was then instructed to speak the words out loud and listen carefully. Under these new instructions, Earl spoke “car”. Following a reflective pause, the researchers heard him say, slowly, “caarr”. Then Earl said “box”, following by a slow “box”. Earl’s excitement grew as he spoke “damp,” now promptly followed by “damp”.

With this astounding recovery, they realized that the brain was able to compensate for this lack of auditory sophistication by actively differentiating the stimuli from the data received from the artificial cochlea. There were also several concurrent trials with different versions of cochlear implants being done, and all had achieved the same result. The only explanation for this is that the brain was able to reconfigure the stimulation from the new device through neuroplastic adaptation. “Those adjustments would presumably require that the brain make hundreds of billions or possibly trillions of new connections!” (Merzenich, 2013, p. 27)

Ultimately, the brain doesn’t care how the information is being presented because of an innate ability to adapt. Merzenich said “it took me a while to realize that the success achieved with these devices was not directly attributable to our clever engineering. All we had done was provide information about complex sounds of human speech to the brain in several different, crudely patterned ways. The plastic brain did most of the real work” (Merzenich, 2013, p. 26). This riveting journey led to the discovery of the key to rendering this device functional.

Neurologic Music Therapy

Neurologic Music Therapy (NMT) is “the therapeutic application of music to cognitive, affective, sensory, language, motor dysfunctions due to disease or injury to the human nervous system” (M. Thaut & Hoemberg, 2016, p. 2). Music from a neurologic perspective can be defined as “complex, temporally structured sound language [that] arouses the human brain on a sensory, motor, perceptive-cognitive, and emotional level simultaneously and stimulates and integrates neuronal pathways in a music-specific way” (Galińska, 2015a, p. 836). In other words, structured auditory stimuli can stimulate multiple domains of brain function and integrate each into a coordinated activity, thereby serving as a useful tool to facilitate therapy and basic education.

An emerging body of evidence suggests how music therapy can influence the development and proper functioning of several domains of brain activity, while also providing a modality with which one can effectively facilitate rehabilitative interventions for a wide range of functions, including motor and speech production. Given the parallels of brain functioning between musical and non-musical behaviors, clinical protocols designed through the Rational Scientific Mediating Model (R-SMM) and administered by a trained music therapist can offer pragmatic, non-invasive, and cost-effective treatment strategies for a wide range of neurological disorders and injuries (L’Etoile et al., 2012). NMT is a branch of music therapy that is founded upon and informed by basic research in the functional neuroanatomy of the human brain and the practice of utilizing auditory stimuli to facilitate neuroplastic therapy (Aldridge, 2005b; Koelsch, 2009; M. H. Thaut, 2010; M. H. Thaut et al., 2015; M. Thaut & Hoemberg, 2016).

Music and the Brain

The processing of auditory stimuli involves a highly complex multidimensional operation. When a sound wave is generated, it ripples out in all directions. The outer ear, also called the pinna, serves to capture these sound waves. They then enter the ear canal where it beats upon the tympanic membrane like a drum. This stimulation then transmits to the three smallest bones in the human body; the malleus (hammer), incus (anvil), and the stapes (stirrup). This transmission initiates the three bones to vibrate within the middle ear which serve to amplify and transfer the input to the inner ear through the vestibular window to the cochlea (Peterson et al., 2022).

The cochlea, a spiral-shaped bone in the inner ear, contains liquid (perilymph) and a range of mechanically sensitive hair cells (stereocilia). Specific stereocilia move in response to specific frequencies. The hairs toward the beginning of the cochlea respond to high frequency sounds, and the hairs toward the center respond to low frequencies (Casale et al., 2022). The mechanical movement of hair cells are then converted to electrical signals sent to the auditory nerve (Simon et al., 2009).

The auditory nerve passes through a series of nuclei within the brain stem. One brain stem structure that is especially relevant to the practice of NMT is a circuit called Central Pattern Generator, which serve to couple incoming auditory stimuli with the appropriate motor movements without any input from higher brain structures. This is why one can begin moving to the beat of a song without realizing it, and is a function NMT practitioners regularly exploit in the process of motor rehabilitation (M. Thaut & Hoemberg, 2016).

The information is then sent to the cortical structures, where higher level processing takes place. Music affects the brain in a special way because both the perception and production of music requires the activation and coordination of a plethora of structures that mediate sensory, cognitive, motor, emotional, and visual functions (Galińska, 2015).

The Rational Scientific Mediating Model (R-SMM)

Rational Scientific Mediating Model (R-SMM) is a mechanism for creating effective music therapy interventions using basic research evidence to identify parallel brain processes between musical and non-musical behaviors (L’Etoile et al., 2012). This process establishes the best scientific foundation with which to carry out applied research and clinical protocols. The R-SMM serves to identify and target the underlying mechanisms through which music can influence and facilitate human behavior in order to formulate the most effective paradigms for patient care. Basic research is a foundational practice of cultivating knowledge on fundamental aspects of human behavior. In the field of music therapy, it may focus on how musical skills are developed and the physiological mechanisms that enable one to perceive and produce music. Basic research in the context of non-musical behavior might be examining the functional neuroanatomy of a given brain part, and the neurophysiological mechanisms of a given behavior such as speaking or walking.

Applied research is concerned with addressing a practical issue. For example, in the context of music therapy, applied research might be evaluating the efficacy of a music therapy protocol that targets a specific brain function. A 2018 study examining the effect of Rhythmic Auditory Stimulation (RAS) concluded that the protocol helped to significantly reduce the frequency of falling in individuals with Parkinson’s disease while effectively modifying key gait parameters such as velocity and stride length. Whereas basic research is about collecting data on general phenomena, applied research is used to apply that knowledge to real-world situations. Basic research serves as a foundation with which to conduct applied research. The R-SMM brilliantly guides the process of exploiting the underlying mechanisms of a given activity and facilitating that behavior with musically-oriented clinical treatment methods that are founded upon a stable scientific foundation.

In music therapy research, one must first understand a given musical behavior through a neuroscientific lens; how that activity affects, impacts, or facilitates brain function. One must also understand a given non-musical behavior through the same lens. A researcher will then identify the correlations in brain function between the musical and non-musical behavior. Once this connection has been established, one may be able to design a treatment protocol that targets a non-musical function through musical activities. The understanding of isomorphic correlations provides a foundation for understanding how musical activity might influence or facilitate non-musical brain function and behavior.

Four sequential levels of scientific inquiry in R-SMM:

Level I: Musical Response Models: Neurological, physiological, and psychological foundations of musical behavior

Level II: Nonmusical Parallel Models: Processes in nonmusical brain and behavior function

Level III: Mediating Models: Influence of music on nonmusical brain and behavior function

Level IV: Clinical Research Models: Therapeutic effects of music

Example of the R-SMM procedure:

Research question: What is the effect of Rhythmic Speech Cueing Protocol on speech intelligibility in patients with dysarthria due to Parkinson’s Disease?

Level I: We are first seeking to understand how musical activities affect neuroanatomical structures involved in perceiving and responding to rhythmic stimuli. Brain imaging suggests that when a healthy adult listens and finger-taps to music, there is a significant activation in the basal ganglia, particularly the globus pallidus (Penhune et al. 1998). More recent research suggests the bilateral activation of several structures within the basal ganglia, including the putamen, pallidum, and caudate nucleus (Grahn & Brett, 2007). This research suggest that perceiving and producing music involves structures within the basal ganglia, the center of Parkinson’s dysfunction. (Jankovic, 2008).

Level II: This level serves to explore and identify the brain functions involved in a non-musical activity, which is speech intelligibility. Having various connections with the motor cortex, basal ganglia structures play a significant role in planning, initiation, and coordination of speech movements (Weismer, 2007). Cell damage and death commonly observed in individuals with Parkinson’s Disease can affect the manipulation of articulatory structures (lips, tongue, etc.) coordinated by the basal ganglia and therefore result in dysfluent and unintelligible speech.

Level III: At this point in the process, one must determine whether these two processes are isomorphic; if there is significant parallel brain functions in both activities. Both rhythm perception and rhythmic execution of speech movements involves priming and activating structures within the basal ganglia (McIntosh et al., 1997). By understanding the underlying mechanisms of both activities, we now have a foundation with which to facilitate the non-musical behavior with musical interventions.

Level IV: Clinical models may now be designed based on the basic research included. Rhythmic Speech Cueing (RSC) is a Neurologic Music Therapy (NMT) technique for facilitating speech production through the use of repetitive rhythmic stimuli (instrumental or vocal music)

The Transformational Design Model (TDM)

Clinical assessment involves facilitating a patient’s level of functioning during intake and throughout the therapeutic experience so a clinician may provide optimal and scientifically valid treatment. The process enables clinicians to (1) provide optimal treatments and (2) to track a patient's progress throughout the therapeutic journey.

In order to effectively conduct clinical assessment, two criteria must be met. The therapeutic applications must (1) be defined and standardized according to some form of consistent treatment protocol and (2) include clinical applications that are supported and validated by the research.

Clinical assessments should adhere to standardized assessment tools, which serve as benchmarks for monitoring and facilitating the therapeutic process. Most assessments are non-musical in nature, and are later used as indications for how to transform a given activity into a musical exercise that addresses non-musical skills and abilities. A music therapist might work in conjunction with an interdisciplinary team of physical therapists, speech therapists, occupational therapists. Therefore, it is important to become familiar with the standardized assessment tools used in each modality.

The TDM is meant to help clinicians translate research findings from the Rational Scientific Mediating Model (RSMM) into functional music therapy practice. The RSMM references basic neuroscience research to identify parallels in neurologic functionality between musical and non-musical skills and behaviors so one might transform a non-musical activity into one that is musical, using music to facilitate neurologic development or rehabilitation. The TDM protocol follows a 6-step process:

1. Diagnosis and functional / clinical assessment of the patient

2. Development of therapeutic goals and objectives

3. Design of functional, non-musical therapeutic exercise structures and stimuli

4. Translation of step 3 into functional therapeutic music exercises

5. Outcome assessment

6. Transfer of therapeutic learning to functional applications for “activities of daily living” (ADL)

All steps in this process are incorporated into typical therapeutic procedures except for step 4. Step 4 is about translating functional and therapeutic exercises, elements, and stimuli into functional therapeutic music exercises and stimuli that are “structured equivalent” to the non-musical exercise.

The TDM is guided by 3 principles:

1. Scientific validity: The translational process must be congruent with and guided by the scientific information developed in the RSMM. The research models between non-musical functions and musical activities must be appropriately connected

2. Musical logic: Musical activities must conform to the aesthetic and artistic principles of good musical form

3. Structural equivalence: The neurologic activity facilitated in the therapeutic music must be isomorphically connected to the non-musical functions.

In conclusion, The R-SMM provides a framework with which one can design clinical protocols with musical stimuli. It facilitates the process of analyzing basic research, conducting applied research, and designing treatment models that are informed and validated by the science. Built upon the foundation of the R-SMM, the TDM is used to design interventions for a specific context to ensure that the musical activity will facilitate the rehabilitation or habilitation of a given non-musical activity, thereby helping an individual to succeed in ADL. This process is crucial for developing clinical protocols that are informed and validated by the neurological mechanics of musical and non-musical behaviors, and serves to further legitimize the profession of music therapy as an effective and evidence-based practice.

Rhythmic Auditory Stimulation (RAS) for Stroke Rehabilitation

A common objective in post-stroke recovery includes gait rehabilitation. The gait cycle or stride a basic unit for gait. It is a series of movements one performs to enable locomotion, which includes the swing and stance phases throughout the alternating use if each leg as a full revolution from right to left leg. Gait is measured in terms of time and distance. The Rhythmic Auditory Stimulation (RAS) protocol for Neurologic Music Therapy (NMT) involves an initial assessment of an individual’s gait. The units to measure within gait is cadence, velocity, and stride length. Cadence refers to the number of steps a person takes in a minute. It can be calculated by the formula: 60/Time x number of steps.

Velocity refers to the speed at which someone walks. Velocity is calculated by the following formula: Velocity = 60/Time (in seconds) x 10 meter (distance)

Finally, Stride length refers to the length of stride on each side of the body. Stride length is calculated by the following formula: (velocity/cadence x2 = Stride length).

Human mobility is controlled by a variety of processes in the nervous system. Sub-cortical functions within the mid-brain and brainstem serve to facilitate autonomic maintenance of posture and arousal, while higher cortical functions such as the motor cortex and SMA serve to manage controlled movements. Individuals with brain injury from stroke often exhibit motor impairment as a result of their injury to various areas that facilitate controlled motor movement such as the BG, Pre-SMA/SMA. RAS is a protocol that is meant to target the process of motor control on all levels of functionality by providing auditory stimuli. As seen in the experiments done by Thaut et al, a given stimulus can facilitate more precise movements needed in the motor rehabilitation process. The RAS protocol for gait rehabilitation includes 6 step process: 1. Assessment of current gait parameters 2. Resonant frequency entrainment and pre-gait exercises with auditory stimuli 3. Frequency modulation at increments of 5-10% 4. Advanced gait exercises on stairs, turns, multi-dimensional surfaces, etc. 5. Fading of musical stimulus and 6. Reassessment of gait parameters. This step is meant to ensure the progress is generalized and applied to daily life skills. This protocol serves to scaffold the process of motor rehabilitation by providing an auditory stimulus, which research has shown to help facilitate the motor activation and coordination.

Educational Applications

Huberman’s “Plasticity Super-Protocol”

As stated above, the process of learning involves conscious focus and deep rest, something that can very plausibly be facilitated. The following protocol has been shared by Dr. Andrew Huberman from Stanford University (Logitech, 2021). Here, he explains that this is an evolving procedure that will surely be modified and enhanced with the introduction of new knowledge and insights. This protocol is informed by the science of brain plasticity and can be applied to both therapeutic and educational situations.

1. Get alert

Without alertness, there is no learning. There are many ways to arouse an individual, and is surely partly contextual. Personal consideration of the student population is recommended.

There is also evidence that background noise, specifically white noise, can help to raise levels of alertness. “White noise, or a white noise background, can shift certain aspects of the circuitry in the brain related to alertness.”(Logitech, 2021, sec. 28:25). These brain areas include the reticular activating system, which “extensively modulates cortical excitability, both in physiological conditions (i.e., sleep-wake cycle and arousal) and in disease (i.e., epilepsy)” (Faraguna et al., 2019, p. 1).

There is a substantial evidence that music (consciously organized auditory stimuli) can also be used to stimulate arousal (CITE).

In a control study investigating the learning of novel vocabulary words, the group that listened to white noise demonstrated superior recall accuracy over time, which was not impacted by participant attentional capacity (Angwin et al., 2017).

2. Get focused

Alertness is a prerequisite to focus. Once arousal levels have been stimulated, the next step is to facilitate focus and motivation. One technique Huberman offers is to instruct the student to gaze at a point in front of them, particularly at the distance at which they will be learning. This, according to Huberman, exploits circuits within the brain that mediate focus and primes the brain to engage in any subsequent activity within those spatial parameters.

The combination of alertness and focus “gives us the ever-elusive motivated state”(Logitech, 2021, p. 28:40).

3. Generate repetitions

Repetition helps to reinforce the learning, so practice making as many repetitions as you can as safely as possible. An additional technique is to gradually modify the repetitions in various ways. As mentioned before, the amplifying action of NE is attenuated with non-variant input. By varying the information in slightly different ways before it becomes monotonous, you are optimizing the integration of information. This practice of gradual variation also helps to facilitate differentiation so one can develop a highly articulated “map” of whatever they are learning.

4. Expect and embrace errors

Huberman states in his presentation that the errors one makes throughout a learning process will increase levels of alertness and focus. “Errors in an attempt to complete something creates heightened levels of activity in the networks of and related to the prefrontal cortex that in essence increase one’s ability to focus” (Logitech, 2021, p. 32:30). If one were to throw darts at a target and miss, there would likely be an increased motivation to succeed in the subsequent throw compared to if one were to hit the bull’s eye. If the brain perceives an error, an alarm will go off prompting one to evaluate the action and rearticulate the information. In essence, one can learn to leverage the inevitable occurrence of errors to facilitate their learning process.

5. Randomly inserted gaps of micro-rest (10-30 seconds)

As mentioned, periods of brief NDSR will serve to reinforce the learning process. This can be done by simply pausing the lesson, closing your eyes, and suspending closely attended behavior and motor commands. Allowing a brief rest will result in increased neural repetitions which help to consolidate the information.

6. Use random intermittent reward

This is best done in random intervals, so the brain does not learn to expect the reward. “If there is an expected reward, it diminishes the capacity for focus” (Logitech, 2021, p. 34:06). A student’s learning will be undermined if they anticipate a reward during or after a lesson. This is informed by a neurophysiological phenomenon called the Dopamine Reward Prediction Error (Schultz, 2016). This theory poses that the more regularly one expects a reward, the more potent that reward has to be in order to remain effective at generating effort. Ultimately, rewards can be a great way to incentivize oneself or one’s students. However, it is not pragmatic to work particularly for the reward.

7. Limit learning to 90-minute sessions or less

Focus and concentration are very expensive, requiring a substantial amount of metabolic energy. The brain’s metabolic activity goes in an oscillatory manner called the Ultradian Rhythm (Spiga, 2017). The ultradian cycle is a biological rhythm that dictates how one’s body functions in time. This cycle goes in 90-minute intervals followed by a 20-minute cool-down period. It is wise to consider this biological cycle in order to optimize the productivity of one’s learning.

8. 10 to 30-minute post-learning NSDR

As mentioned, periods of rest after a learning session will help to consolidate the information. This step facilitates the completion of the ultradian cycle. The 10-30 minute NSDR can come in the form of a power nap, going outside and allowing the mind to wander, enjoying a cup of water, eating a snack, meditation, hypnosis, or any other rather mindless task that doesn’t require closely attended behavior.

9. Maximize quality of sleep

As mentioned before, proper quality and quantity of sleep is crucial in the learning process. It would be wise to maximize your ability to rest by following the tips offered by Huberman in his podcast (Huberman, 2021).

Conclusion

In conclusion, this brief analysis regarding the burgeoning information of neuroplasticity provides a theoretical framework and practical applicability for facilitating both learning and therapy. There are several modalities that can be used to facilitate neuroplastic therapy, and we would benefit by incorporating an interdisciplinary coordination to further galvanize the practice. Music therapy is a promising modality for neuroplastic therapy because it engages the brain in a very special way. Perceiving and producing auditory stimuli requires the activation and coordination of a multitude of brain functions and structures.

With an evolving understanding of the neurochemical mechanics of brain plasticity, we might be able to conduct therapy and education in order to maximize the efficiency of the practice. This information enables us to use these tools to recover and advance our skills and capacities, and possibly transcend human ability.

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