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The Role of Dendritic Spine Density in Neuropsychiatric and Learning Disorders
Photo originally by MethoxyRoxy on Wikimedia Commons. No changes. CC License BY-SA 2.5.
By Neha Madugala, Cognitive Science, ‘21
Author’s Note: Last quarter I took Neurobiology (NPB100) with Karen Zito, a professor at UC Davis. I was interested in her research in dendritic spines and its correlation to my personal area of interest in research regarding the language and cognitive deficiencies present in different populations such as individuals with schizophrenia. There seems to be a correlational link between the generation and quantity of dendritic spines and the presence of different neurological disorders. Given the dynamic nature of dendritic spines, current research is studying their exact role and the potential to manipulate these spines in order to impact learning and memory.
Introduction
Dendritic spines are small bulbous protrusions that line the sides of dendrites on a neuron [12]. Dendritic spines serve as a major site of synapses for excitatory neurons, which continue signal propagation in the brain. Relatively little is known about the exact purpose and role of dendritic spines, but as of now, there seems to be a correlation between the concentration of dendritic spines and the presence of different disorders, such as autism spectrum disorders (ASD), schizophrenia, and Alzheimer’s disease. Scientists hypothesize that dendritic spines are a key player in the pathogenesis of various neuropsychiatric disorders [8]. It should be noted that other morphological changes are also observed when comparing individuals with the mentioned neuropsychiatric disorders are compared to neurotypical individuals. However, all these disorders share the common thread of abnormal dendritic spine density.
The main disorders studied in relation to dendritic spine density are autism spectrum disorder (ASD), schizophrenia, and Alzheimer’s disease. Current studies suggest that these disorders result in the number of dendritic spines straying from what is observed in a neurotypical individual. It should be noted that there is a general decline in dendritic spines as an individual ages. However intellectual disabilities and neuropsychiatric disorders seem to alter this density at a more extreme rate. The graph demonstrates the general trend of dendritic spine density for various disorders; however, these trends may slightly vary across individuals with the same disorder.
Dendritic Spines
I. Role of Dendritic Spines
Dendritic spines are protrusions found on certain types of neurons throughout the brain, such as in the cerebellum and cerebral cortex. They were first identified by Ramon y Cajal, who classified them as “thorns or short spines” located nonuniformly along the dendrite [6].
The entire human cerebral cortex consists of 1014 dendritic spines. A single dendrite can contain several hundred spines [12]. There is an overall greater density of dendritic spines on peripheral dendrites versus proximal dendrites and the cell body [3]. Their main role is to assist in synapse formation on dendrites.
Dendritic Spines fall into two categories: persistent and transient spines. Persistent spines are considered ‘memory’ spines, while transient spines are considered ‘learning’ spines. Transient spines are categorized as spines that exist for four days or less and persistent spines as spines that exist for eight days or longer [5].
The dense concentration of spines on dendrites is crucial to the fundamental nature of dendrites. At an excitatory synaptic cleft, the release of the neurotransmitter at excitatory receptors on the postsynaptic cell results in an excitatory postsynaptic potential (EPSP), which causes the cell to fire an action potential. An action potential is where a signal is transmitted from one neuron to another neuron. In order for a neuron to propagate an action potential, there must be an accumulation of positive charge at the synapses, reaching a certain threshold (Figure 2). The cell must reach a certain level of depolarization – a difference in charge across the neuron’s membrane making the inside more positive. A single EPSP may not result in enough depolarization to reach this action potential threshold. As a result, the presence of multiple dendritic spines on the dendrite allows for multiple synapses to be formed and multiple EPSPs to be summated. With the summation of various EPSPs on the dendrites of the neurons, the cell can reach the action potential threshold. The greater density of dendritic spines along the postsynaptic cell allows for more synaptic connections to be formed, increasing the chance of an action potential to occur.
Figure 2. Firing of Action Potential (EPSP)
- Neurotransmitter is released by the presynaptic cell into the synaptic cleft.
- For an EPSP, an excitatory neurotransmitter will be released, which will bind to receptors on the postsynaptic cell.
- The binding of these excitatory neurotransmitters will result in sodium channels opening, allowing sodium to go down its electrical and chemical gradient – depolarizing the cell.
- The EPSPs will be summated at the axon hillock and trigger an action potential.
- This actional potential will cause the firing cell to release a neurotransmitter at its axon terminal, further conveying the electrical signal to other neurons.
II. Creation
Dendrites initially are formed without spines. As development progresses, the plasma membrane of the dendrite forms protrusions called filopodia. These filopodia then form synapses with axons, and eventually transition from filopodia to dendritic spines [6].
The reason behind the creation of dendritic spines is currently unknown. There are a few potential hypotheses. The first hypothesis suggests that the presence of dendritic spines can increase the packing density of synapses, allowing for more potential synapses to be formed. The second hypothesis suggests that their presence can help prevent excitotoxicity, overexcitation of the excitatory receptors (NMDA and AMPA receptors) present on the dendrites. These receptors usually bind with glutamate, a typically excitatory neurotransmitter, released from the presynaptic cell. This can result in damage to the neuron or if more severe, neuronal death. Since dendritic spines compartmentalize charge [3], this feature helps prevent the dendrite from being over-excited beyond the threshold potential for an action potential. Lastly, another hypothesis suggests that the large variation in dendritic spine morphology suggests that these different shapes play a role in modulating how postsynaptic potentials can be processed by the dendrite based on the function of the signal.
The creation of these dendritic spines is rapid during early development, slowly tapering off as the individual gets older. This process is mostly replaced with the pruning of synapses formed with dendritic spines when the individual is older. Pruning helps improve the signal-to-noise ratio of signals sent within neuronal circuits [3]. The signal-to-noise ratio outlines the ratio of signals sent by neurons and signals actually received by postsynaptic cells. It determines the efficiency of signal transmission. Experimentation has shown that the presence of glutamate and excitatory receptors (such as NMDA and AMPA) can result in the formation of dendritic spines within seconds [3]. The introduction of NMDA and AMPA results in cleavage of intracellular adhesion molecule-5 (ICAM5) from hippocampal neurons. ICAM5 is a “neuronal adhesion molecule that regulates dendritic elongation and spine maturation. [11]” Furthermore, through a combination of fluorescent dye and confocal or two-photon laser scanning microscopy, scientists were able to use imaging technology to witness that spines can undergo minor changes within seconds and more drastic conformational changes, even disappearing over minutes to hours [12].
III. Morphology
The spine head’s morphology, a large bulbous head connected to a very thin neck that attaches to the dendrite, assists in its role as a postsynaptic cell. This shape allows one synapse at a dendritic spine to be activated and strengthened without influencing neighboring synapses [12].
Dendritic spine shape is extremely dynamic, allowing one spine to slightly alter its morphology throughout its lifetime [5]. However, dendritic spine morphology seems to take on a predominant form that is determined by the brain region of its location. For instance, presynaptic neurons from the thalamus take on the mushroom shape, whereas the lateral nucleus of the amygdala have thin spines on their dendrites [2]. The type of neuron and brain region the spine originates from seem to be correlated to the observed morphology.
The spine contains a postsynaptic density, which consists of neurotransmitter receptors, ion channels, scaffolding proteins, and signaling molecules [12]. In addition to this, the spine has smooth endoplasmic reticulum, which forms stacks called spine apparatus. It further has polyribosomes, hypothesized to be the site of local protein synthesis in these spines, and an actin-based cytoskeleton for structure [12]. The actin-based cytoskeleton makes up for the lack of microtubules and intermediate filaments, which play a crucial role in the structure and transport of most of our animal cells. Furthermore, these spines are capable of compartmentalizing calcium, the ion used at neural synapses that signal the presynaptic cell to release its neurotransmitter into the synaptic cleft [12]. Calcium plays a crucial role in second messenger cascades, influencing neural plasticity [6]. It also plays a role in actin polymerization, which allows for the motile nature of spine morphology [6].
There are many various shapes for dendritic spines. The common types are ‘stubby’ (short and thick spines with no neck), ‘thin’ (small head and thin neck), ‘mushroom’ (large head with a constricted neck), and ‘branched’ (two heads branching from the same neck) [12].
IV. Learning and Memory
Dendritic spines play a crucial role in memory and learning through occurrence of long-term potentiation (LTP), which is thought to be the cellular level of learning and memory. LTP is thought to induce spine formation, which hints at the common correlation that learning is associated with the formation of dendritic spines. Furthermore, LTP is thought to be capable of altering the immature and mature hippocampus, commonly associated with memory [2]. To contrast LTP, long-term depression (LTD) essentially works opposite to LTP – decreasing the dendritic spine density and size [2].
The correlation between dendritic spines and learning is relatively unknown. There seems to be a general trend suggesting that the creation of these spines is associated with learning. However, it is unclear whether learning results in the formation of these spines or if the formation of these spines results in learning. The general idea behind this hypothesis is that dendritic spines aid in the formation of synapses, allowing the brain to form more connections. As a result, a decline in these dendritic spines in neuropsychiatric disorders, such as schizophrenia, can inhibit an individual’s ability to learn. This is observed in various cognitive and linguistic deficiencies observed in individuals with schizophrenia.
Memory is associated with the strengthening and weakening of connections due to LTP and LTD, respectively. The alteration of these spines through LTP and LTD is called activity-dependent plasticity [6]. The main morphological shapes associated with memory are the mushroom spine, a large head with a constricted neck, and the stubby spine, a short and thick spine with no neck [6]. Both of these spines are relatively large, resulting in more stable and enduring connections. These bigger and heavier spines associated with learning are a result of LTP. By contrast, transient spines (live four days or shorter) are usually smaller and more immature in morphology and function, resulting in more temporary and less stable connections.
LTP and LTD play a crucial role in modifying dendritic spine morphology. Neuropsychiatric disorders can alter these mechanisms resulting in abnormal density and size of these spines.
Schizophrenia
I. What is Schizophrenia?
Schizophrenia is a mental disorder that results in disordered thinking and behaviors, hallucinations, and delusions [9]. The exact mechanics of schizophrenia are still being studied as researchers are trying to determine the underlying biological reasons behind this disorder and a way to help these individuals. Current treatment is focused on reducing and in some cases treating symptoms of this disorder, but more research and understanding is required to fully treat this mental disorder.
II. Causation
The exact source of schizophrenia seems to lie somewhere between the presence of certain genes and environmental effects. There seems to be a correlation between traumatic or stressful life events during an individual’s adolescence to an increased susceptibility to developing schizophrenia [1]. While research is still underway, certain studies point to cannabis having a role in increasing susceptibility to schizophrenia or worsening symptoms if an individual already has schizophrenia [1]. There seems to be some form of a genetic correlation, given an increased likelihood of developing schizophrenia if present in a family member. This factor seems to result from a combination of genes; however, no genes have been identified yet. There also seems to be a chemical component, given the variation of chemical composition and density of neurotypical individuals and individuals with schizophrenia. Specifically, researchers have observed an elevated amount of dopamine found in individuals with schizophrenia [1].
III. Relationship between Dendritic Spines and Schizophrenia
A common thread among most schizophrenia patients is an impairment of pyramidal neuron (prominent cell form found in the cerebral cortex) dendritic morphology, occurring in various regions of the cerebral cortex [7]. Observed in postmortem brain tissue studies, there seems to be a reduced density of dendritic spines in the brains of individuals with schizophrenia. These findings are consistent with various regions of the brain that have been studied, such as the frontal and temporal neocortex, the primary visual cortex, and the subiculum within the hippocampal formation [7]. Out of seven studies observing this finding, the median reported decrease in spine density was 23%, with the overall range of these various studies being a decline of 6.5% to 66% [7].
It should be noted that studies were done to see if the decline in spine density was due to the usage of antipsychotic drugs. However animal and human trials showed no significant difference in the dendritic spine density of tested individuals.
This decline in dendritic spine density is hypothesized to be the result of the failure of the brain of schizophrenic individuals to produce sufficient dendritic spines at birth or if there is a more rapid decline of these spines during adolescence, where the onset of schizophrenia is typically observed [7]. The source of this decline is unclear, but seems to be attributed to deficits in pruning, maintenance, or simply the mechanisms of the underlying formation of these dendritic spines [7].
However, there are conflicting results. For instance, Thompson et al. conducted a study that seemed to suggest that a decline in spine density resulted in a progressive decline of gray matter, typically observed in schizophrenic individuals. Thompson et al. conducted an in vivo study of this phenomena. The study used MRI scans for twelve schizophrenic individuals and twelve neurotypical individuals, finding a progressive decline in gray matter – starting in the parietal lobe and expanding out to motor, temporal, and prefrontal areas [10]. The study suggests that the main attribution for this is a decline in dendritic spine density with the progression of the disorder. This study coincides with the previously mentioned hypothesis of a decline of spines during adolescence.
It is also possible that there is a combination of both of these factors occurring. Most studies have only been able to observe postmortem brain tissue, creating the confusion of whether there is a decline in spines or if the spines are simply not produced in the first place. The lack of in vivo studies makes it difficult to find a concrete trend within data.
Conclusion
While research is still ongoing, current evidence seems to suggest that dendritic spines are a crucial aspect in learning and memory. Their role in these crucial functions has been reflected by their absence in various neuropsychiatric disorders – such as schizophrenia, certain learning deficits present in some individuals with ASD, and memory deficits present in Alzheimer’s disease. These deficits seem to occur during the early creation of neural networks in the brain at synapses. Further research understanding the development of these spines and the creation of different morphological forms can be crucial in determining how to potentially cure or treat these deficiencies present in neuropsychiatric and learning disorders.
References
- NHS Choices, NHS, www.nhs.uk/conditions/schizophrenia/causes/.
- Bourne, Jennifer N, and Kristen M Harris. “Balancing Structure and Function at Hippocampal Dendritic Spines.” Annual Review of Neuroscience, U.S. National Library of Medicine, 2008, www.ncbi.nlm.nih.gov/pmc/articles/PMC2561948/.
- “Dendritic Spines: Spectrum: Autism Research News.” Spectrum, www.spectrumnews.org/wiki/dendritic-spines/.
- Hofer, Sonja B., and Tobias Bonhoeffer. “Dendritic Spines: The Stuff That Memories Are Made Of?” Current Biology, vol. 20, no. 4, 2010, doi:10.1016/j.cub.2009.12.040.
- Holtmaat, Anthony J.G.D., et al. “Transient and Persistent Dendritic Spines in the Neocortex In Vivo.” Neuron, Cell Press, 19 Jan. 2005, www.sciencedirect.com/science/article/pii/S0896627305000048.
- McCann, Ruth F, and David A Ross. “A Fragile Balance: Dendritic Spines, Learning, and Memory.” Biological Psychiatry, U.S. National Library of Medicine, 15 July 2017, www.ncbi.nlm.nih.gov/pmc/articles/PMC5712843/.
- Moyer, Caitlin E, et al. “Dendritic Spine Alterations in Schizophrenia.” Neuroscience Letters, U.S. National Library of Medicine, 5 Aug. 2015, www.ncbi.nlm.nih.gov/pmc/articles/PMC4454616/.
- Penzes, Peter, et al. “Dendritic Spine Pathology in Neuropsychiatric Disorders.” Nature Neuroscience, U.S. National Library of Medicine, Mar. 2011, www.ncbi.nlm.nih.gov/pmc/articles/PMC3530413/.
- “Schizophrenia.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 7 Jan. 2020, www.mayoclinic.org/diseases-conditions/schizophrenia/symptoms-causes/syc-20354443.
- “Schizophrenia and Dendritic Spines.” Ness Labs, 20 June 2019, nesslabs.com/schizophrenia-dendritic-spines.
- “Synaptic Cleft: Anatomy, Structure, Diseases & Functions.” The Human Memory, 17 Oct. 2019, human-memory.net/synaptic-cleft/.
- Tian, Li, et al. “Activation of NMDA Receptors Promotes Dendritic Spine Development through MMP-Mediated ICAM-5 Cleavage.” The Journal of Cell Biology, Rockefeller University Press|1, 13 Aug. 2007, www.ncbi.nlm.nih.gov/pmc/articles/PMC2064474/.
- Zito, Karen, and Venkatesh N. Murthy. “Dendritic Spines.” Current Biology, vol. 12, no. 1, 2002, doi:10.1016/s0960-9822(01)00636-4.
Cerebral Palsy: More Than a Neurological Condition
By Anjali Borad, Psychology ‘21
Author’s Note: This paper explores the dynamic relationship between a mother and her son and the complexity of a health condition that the son has. I will look at a specific case of cerebral palsy—my brother—and talk about how his condition came to be and the likely prognosis. I want to delve into the details of how family dynamics play a very important role in the caregiving and caretaking that goes along with having a disabled family member and how that is seen in the relationship between my brother and my mother.
I see two different perspectives of my brother, Sam, and his condition, cerebral palsy: one through his eyes and the other through the eyes of my mother, his caregiver. Observing how my mother has taken care of Sam from the beginning, I began to realize that it takes a lot to be a caregiver and that she plays a significant role in his life. In order to gain more insight into her practices of giving care, I interviewed her. I started off by asking her what it means to be a caregiver and what “care” means to her. She took a deep breath in and expressed her daily routines as a caregiver. “Waking up in the morning, the first thing that you have to do is to attend to him and care for him before yourself,” she said. “You know that from brushing his teeth to giving him a shower and feeding him, we have to do everything from A to Z.”[1] A day in the life of my mother starts and ends with my brother, from getting him out of bed to providing him with basic needs like food and water. She even takes care of specific requests that pertain to his own interests, such as wearing a watch every day and having matching socks and pants.
Cerebral palsy is a neurological disorder. Most cases of cerebral palsy occur under hypoxic conditions during the birthing process. This lack of oxygen to the brain can cause developmental delays and lifelong debilitating conditions [2]. My family and I have experienced the difficulties and limitations that accompany this disease first hand. My brother’s condition of cerebral palsy is in its most extreme form: he has quadriplegia and spasticity. A telltale sign of quadriplegic cerebral palsy is the inability to voluntarily control and use the extremities. Spasticity occurs due to a lesion in the upper motor neuron, located in the brain and spinal cord. It interferes with the signals that your muscles need to move and manifests in the body by increasing muscle tone and making the muscles unusually tight [3]. Dr. Neil Lava, a member of the National Multiple Sclerosis Society and American Academy of Neurology, describes the pathophysiology of a lack of muscular activity. “When your muscles don’t move for a long time, they become weak and stiff,” Lava writes [4]. This physical restraint is evident in my brother’s case because he has been wheelchair-bound since the age of seven.
Upper motor neuron lesions can worsen over time. Major prolonged symptoms include over-responsive reflexes, weakness in the extensor muscles, and slow movement of the body, all of which affect the sensation of balance and coordination. For this kind of condition, occupational and physical therapy can alleviate some of the symptomatic stresses. In the case of therapy, performing the right kind of stretches can help to relax some muscle stiffness. Medication and certain surgical procedures can also treat upper motor neuron symptoms. Some common muscle relaxants prescribed to patients are Zanaflex, Klonopin and Baclofen [5].
At the neurochemical level, “Spasticity results from an inadequate release of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the central nervous system,” according to Mohammed Jan [6]. In a normal neural cell, when GABA interacts with and binds to GABA receptors on the postsynaptic neuron, it decreases the likelihood that the postsynaptic neuron will fire an action potential because of the inhibitory nature of GABA receptors. For a condition like cerebral palsy in which some form of insult or damage has occurred to the brain, especially in the upper motor neurons, the result is hyperactive reflexes (as opposed to the calming sensation). At this point, muscle spasticity begins to become detectable. [6]
Apart from the biological mechanism underlying this condition, particularly significant environmental factors also gravely contributed to Sam’s condition. For eight months, my mother was carrying a normally developing fetus in the womb. However, a few weeks before Sam’s delivery date, my mother could not feel any fetal movement for about three days, so she went to check on it. As she was receiving the examination, Sam unexpectedly made a fluttering movement. If he had not moved, my mother would have had to get a Caesarean section immediately. Since he moved inside, the examiners found nothing to be wrong with the fetus and deemed it safe to send my mother home.
Just a few days later, my mom was rushed to the hospital after her labor pain started. At the time, the primary medical staff mostly consisted of medical interns still honing in on decision-making skills during critical situations. From the time of my mother’s arrival at the hospital, 13 hours passed before a team of doctors and interns determined that she needed a C-section. Once this decision was made, additional time was required by the medical professionals to prepare the room for surgery. All the while, my mom was in labor pain and, unbeknownst to her, the fetus had become separated from the placenta while the umbilical cord suffered damage. By the time the surgery finally ended, Sam had suffered from asphyxiation. According to the Cerebral Palsy Guide, “asphyxiation that occurs during labor or delivery may have been caused by medical malpractice or neglect. Early detachment of the placenta, a ruptured uterus during birth or the umbilical cord getting pinched in a way that restricts blood flow can cause oxygen deprivation.” [7]
The most important aspect of a disease, once established and diagnosed, is treatment and therapy. Asking questions about how to manage pain, how to make daily routines easier to perform, and how to accommodate family members in raising a child with a disability all goes into the planning process of treatment as well. These individuals need more than mere pills in order to get through their daily lives. This is where therapists (i.e. occupational, behavioral, speech, physical, and vocational therapists) and related health advocates, including family members, come into play. While therapists cannot completely remove the condition, they provide a strategy to alleviate psychological symptoms, including feelings of loneliness, fear of who will care for you, or resentment towards oneself. Family psychologists can help children with cerebral palsy by providing an initial assessment in an attempt to gain more insight into the family dynamics. If there seems to be a lack of parental support or lack of child attachment, a family psychologist can address this through therapy sessions with the parents. Therapy sessions allow for parents to individually discuss what they think is working well for the child and other areas that can be improved. The parents are also free to talk about their own personal issues, permitting the psychologist to gain a better understanding of certain triggers for the parents. These triggers can affect caregiving for the child with special needs.
Cerebral palsy is more than just a neurological condition. It is a way of life that, for Sam, is entangled in a web of personal, social, familial, caregiver and medical challenges. One noteworthy concept heavily emphasized in the healthcare field today is the importance of a family-centered management model. The notion of a family-centered approach strives to improve the way of life for individuals with the condition in the family in a mutual way. For a family, it can be quite taxing physically and emotionally to have to take care of someone for the rest of their lives. While it is considerably easier for the receiver to reap the benefits of the caregiver, it is more difficult for the caregiver to constantly provide. The family-centered approach tries to find a middle ground where the caregiver or family and the care-receiver are benefitting from each other as much as possible. In a holistic family-centered model, the needs of each family member are taken into consideration.
A study by Susanne King details the role of pediatric neurologists, therapists, and family members, especially parents, in caring for children with cerebral palsy. This study mainly emphasizes the limiting restraints cerebral palsy places on individuals. For example, families with special needs children often have specific ways of communicating, specialized equipment used at home, and a support system consisting of the family members, therapists, and guidance counselors. The heavy emphasis on familial involvement with medical guidance from professionals is the root of family-centered care. King describes that “these children often have complex long-term needs that are best addressed by a family-centered service delivery model.”[8] Oftentimes, we see that those families who have disabled family members are suffering. Some parents, for example, experience great distress because they do not completely understand what is happening to their child and, thus, fail to acknowledge their limitations at times. Others feel that they are incapable of looking after their child but cannot bear the idea of sending them away to an institution.
King also discusses the lack of investigation of families as a whole practicing care-giving. “Although there is much evidence supporting a family-centered approach in the area of parental outcomes, there has been little work reported on the family unit as a whole,” King writes. “The most common outcome is better psychological well-being for mothers (because they generally were the participants in most of the studies).”[8]
In my family, I can actively see family-centered management of my brother’s condition occurring. I see how both my parents have certain roles in my brother’s life that collectively enable or mobilize him to feel included and respected. I like to call my parents the arms and legs for my brother in a figurative sense, and I like to call myself the eyes for my brother. Working together to the best of our ability, we enable him to see the outside world in a way that’s similar to the way we experience it.
All my life, I have seen my mother perform the role of a caregiver. I have seen so many ups and downs in her situation, and I would always ask myself the following questions. What makes her get up every morning and continue to give the care she does? What makes her not give up? She told me, “I have faith in God, and I know that He creates pathways for me to deal with the physical implications of taking care of a disabled family member and see, I have never had any major problems with your brother. I will continue to give care for as long as my body will allow for me to do so.”[1] Annemarie Mol and John Law of Duke University collaboratively published a research paper detailing how people are more than just the definitions of their disorders or conditions. According to Mol and Law, people actively create and construct their life in a way that either enhances or minimizes the intensity of their conditions. Mol and Law also explain that “there are boundaries around the body we do…so long as it does not disintegrate, the body-we-do hangs together. It is full of tensions, however.”[9] Their conclusion on what makes a person pull through encapsulates the reason my mother still continues to care for my brother.
The definition of cerebral palsy as a condition is very limited. Oftentimes people who have debilitating conditions are missing a network or a support system of people, that once established, can essentially improve that family member’s way of life. With the family-centered approach to managing care, one is essentially enabling the disabled family member by actively being a part of their life, including their day-to-day life activities. For example, through the support system we provide for Sam, he can feel that he is in good hands and that he has established emotional and personal security. Although his condition is permanent, it is comforting to know that our family dynamics allow for an environment in which he can thrive while remaining mentally healthy.
References
- Borad, Geeta. “Practices of Care, Interviews.” 8 Dec. 2018.
- Debello, William, and Lauren Liets. “Motor Systems.” Lecture, NPB 101, Davis, CA, 20 Jan. 2020.
- Emos MC, Rosner J. Neuroanatomy, Upper Motor Nerve Signs. [Updated 9 Apr. 2020]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 January. https://www.ncbi.nlm.nih.gov/ books/NBK541082/
- Lava, Neil. “Upper Motor Neuron Lesions: What They Are, Treatment.” WebMD, 11 May 2018, https://www.webmd.com/multiple-sclerosis/upper-motor-neuron-lesions-overview#1.
- Chang, Eric et al. (2013). “A Review of Spasticity Treatments: Pharmacological and Interventional Approaches.” Critical reviews in physical and rehabilitation medicine vol. 25, 1-2: 11-22.
- Jan, Mohammed M S. (2006). “Cerebral palsy: comprehensive review and update.” Annals of Saudi Medicine. vol. 26, 2.
- Cerebral Palsy Guide. “Causes of Cerebral Palsy – What Causes CP.” Cerebral Palsy Guide. 21 Jan. 2017, https://www.cerebralpalsyguide.com/cerebral-palsy/causes/.
- King S, Teplicky R, King G, Rosenbaum P. (2004). “Family-centered service for children with cerebral palsy and the families: a review of the literature.” Semin Pediatr Neurol. Science Direct.
- Mol, A & Law, J. (2004). “Embodied Action, Enacted Bodies: the Example of Hypoglycaemia.” Body & Society, 43–62.
A Regenerative Cocktail: Combination of Drugs Promotes the Conversion of Glial Cells to Neurons
By Reshma Kolala, Biochemistry & Molecular Biology ‘22
Author’s Note: While browsing recent findings in Neuroscience, I came across research investigating the possible conversion of glia to neurons. Although the conventional idea that neurons are irreplaceable has been overturned in multiple research studies, I was immediately intrigued by the possibility for neighboring glia to be the source of neural regeneration. The implications of this research could completely transform how treatment is approached in the neuroscience field of medicine.
This is Your Brain on Music
By Timur Katsnelson, Neurobiology, Physiology, and Behavior, ‘19
Author’s Note: Like everyone else, I love music- especially the works of my favorite artists. There is nothing better than listening or jamming out to your favorite song. The human love for music is a powerful binding force, but why do we even like it? What are the underlying physiological responses of our enjoyment? I wanted to explore the functions of our brain as they relate to enjoying music, and found some interesting results about what scientists have uncovered thus far.
One of the most distinguishing characteristics of the human brain is the ability to interpret and feel emotions regarding complex environmental stimuli such as visual arts and music. Even more interesting is the seemingly infinite amount of variation in how each individual perceives these stimuli, or rather, the reason why one person may love to listen to Vampire Weekend while another casually listens to a lo-fi playlist. There are structural similarities shared by all humans, crafted over millions of years of evolution, but they do not account for different tastes. Neuroscientists who study dopaminergic pathways and other neural structural mechanisms have made several initial steps in understanding what physiological functions music serves to humans. So far, it has been established that musical appreciation and preference are related to the connectivity of white matter between regions in the auditory cortex and the regions processing emotion; variations in activity from neurons related to emotional communication could explain our differences in musical taste. Answering questions about the effects of music on the brain will undoubtedly help to answer larger questions about music’s evolutionary purpose and its profound impact on human cultures.
Neuroscience of Pleasure and Reward
Motivation, emotion, and arousal can all be attributed to elevated activity in the reward centers of the brain. As these traits are known to have implications in addiction, their cellular manifestations have been studied for several decades. The ventral striatum, midbrain, amygdala, and some areas of the prefrontal cortex have all been demonstrated, in varying degrees, to being recruited in instances of drug use. The dopaminergic pathways of the brain refer to a series of densely-packed neuronal connections that are stimulated by the neurotransmitter dopamine to propagate signals. Collectively, these regions of the brain are responsible for our response to natural stimuli and our actions to either seek or avoid them.
The brain’s reward centers are also known to be active in communal interactions, suggesting that there is a benefit to acting in a socially-positive way. Interestingly, the emotions experienced by humans when listening to their favorite music is correlated to the engagement of the same dopaminergic pathways as those that are stimulated during drug use or social interactions. It is important to note that the similarities between which parts of the brain are engaged when listening to music, using drugs, or being with people do not imply that the physiological or psychological effects are closely mimicked in the process. Neurons communicate via action potentials. These synaptic changes in membrane voltage effectively signal messages to neighboring neurons, but nothing about them is inherently meaningful. Since all action potentials are the same, it is the frequency of their appearances that convey messages. As it relates to the similarities in regions activated by both drug use and music, increases in activity do not necessarily equal the same frequencies of action potentials. Nonetheless, positron emission tomography (PET) scans observing pleasurable responses to music in animals and humans show the same regions of the brain being activated. Increases in dopaminergic pathway activity in the nucleus accumbens (NAc), ventral pallidum, ventral tegmental area, amygdala, hippocampus, and other areas of the midbrain collectively correlate to the reward process [3].
The Brain’s Response to Music
There are several experiments that examine the neural response to music, or “aesthetic responses” as some scientific literature has described. PET studies visualized the neural relationship with ‘intensely pleasurable’ responses to music [2]. Intensely pleasurable responses are defined as euphoric sensations in reaction to music, characterized by “shivers-down-the-spine” or “chills” [1]. In addition to observing activity levels within the brain, researchers monitored heart rate and blood flow in the brain. When excited by external stimuli, the central nervous system commands a response throughout the body to heighten the senses and increase awareness. A study by Blood et al. measured heart rate and cerebral blood flow of subjects listening to chill-inducing songs. Increases in the intensity of stimulation from a song were shown to increase blood flow in areas of the brain’s reward centers, as well as the heart rate. It is known that pleasure derived from music activates regions between the brain’s auditory region, specifically the superior temporal gyrus, and the reward centers such as the ventral and dorsal striatum. Parts of the basal ganglia, the ventral and dorsal striatum are largely responsible for motor function as it relates to desire and reward. Despite these findings, the exact connection between physiological sensations and aesthetic responses in the brain are ambiguous [1].
Evolutionary Advantage?
The question of music’s evolutionary purpose has been postulated for over a century, including in Darwin’s The Descent of Man, and Selection in Relation to Sex [3]. To some experts, music is considered to be the result of an evolutionary exaptation. That is, music’s purpose was not selected for its current use by humans. Rather, it came about as a result of excited neural pathways that engage emotional responses [1]. Others suggest that music is an important communicative tool that possibly preceded speech and language [5]. In this case, the chills elicited by music are physiologically measurable emotional responses, which signify that music is effectively a resource for communicating emotions [3].
Based on this idea, some researchers wanted to examine responses to music between individuals and compare them to the structural foundations of their emotional expressiveness capacity. Musical anhedonia is used to describe a condition for those who do not exhibit any pleasure from music, as there is no dopaminergic response from the reward centers. The flat affective response of individuals with this condition could be compared to the brains of subjects with affective responses to music. One such study found that patterns of white matter networks between the superior temporal gyrus through the ventral and dorsal striatum predicted the amount of reward response elicited by music. As the name suggests, the superior temporal gyrus is part of the temporal lobe- which is associated with the auditory cortex. This path of white matter moves from the auditory processing system to the basal ganglia. The aforementioned ventral and dorsal striatum, both parts of the basal ganglia, are involved in motor function. However, there could be other reward-related responses elicited from these structures, such as chills. Some researchers postulate that music may have had its origins from chill-responses to pleasurable sounds in the evolutionary environment, which may have motivated our ancestors to create their own response-evoking sounds [3]. Chills are viewed as a form of communication, demonstrating a positive response to sounds. Therefore, finding this white matter network may suggest that, in addition to emotion, there is a structural aspect of music involved in communication [3].
Music’s Effect on Other Species
A less studied and even less understood aspect of music is its meaning and interpretation by other species. Understanding the effect of music on other animals could provide a glimpse into music’s inherent biological meaning. Although it is clear that the pleasures that humans experience from music are not necessarily akin to the experience of animals, research suggests that music genres can affect the mood or behavior of captive animals. Country music has been shown to improve the mood and well-being of cattle, as opposed to more harsh or erratic-sounding music such as rock and jazz. One study specifically showed that cows more readily entered milking parlours when exposed to country music. However, these foundational animal studies have strictly been observant of the behavior and activity of the cattle [4]. Examining the neurological differences in musical preference or indifference in cattle would provide more concrete evidence of the neurological change that leads to the observed behaviors.
Further Discussions and Research
The research discussed thus far provides clues into the baseline purposes of music and the nature of its evolutionary impact. Yet, there are still many interesting existential discussion topics surrounding the origins of music and its purpose. Grounded biological inquiry, however, will be the most essential tool to get closer to understanding the extraordinary impact of music on human culture, communication, and evolution. Moving forward, researchers should continue to address the differences between individual preference and capacity to respond to music by studying differences in neural matter and structure. Most evidence suggests that music has a strong correlation to emotional expression, so examining the mechanisms of communication and interpreting abstract stimuli as emotional cues will help researchers understand how music can be physiologically deciphered and responded to. On a broader scale, examining global differences in musicality could provide insight into how different cultures and languages relate to their historically popular forms of music and rhythms. Could phonetic or rhythmic patterns in language correspond to preferences for certain tempos, measures, rhythms, or lyrics in music? These questions would be better served in a separate discussion but for now, go back to enjoying your favorite song.
References:
- Blood, A. J., & Zatorre, R. J. (2001). Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion. Proceedings of the National Academy of Sciences of the United States of America, 98(20), 11818-23.
- Matthew E. Sachs, Robert J. Ellis, Gottfried Schlaug, Psyche Loui (2016). Brain connectivity reflects human aesthetic responses to music, Social Cognitive and Affective Neuroscience, Volume 11, Issue 6, Pages 884–891.
- Psyche Loui et al. (2017). White Matter Correlates of musical Anhedonia: Implications for Evolution of Music. Frontiers in Psychology, Volume 8, Article 1664.
- Deborah L. Wells (2009). Sensory Stimulation as Environmental Enrichment for Captive Animals: A Review. Applied Animal Behaviour Science. Volume 118, Issues 1-2, Pages 1-11.
- Steven Mithen (2007). The Singing Neanderthals: The Origins of Music, Language, Mind, and Body.
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Author’s Note
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