Dr. David Linden: Life, Death & the Neuroscience of Your Unique Experience

Podcast Host: Dr. Andrew Huberman (Stanford Associate Professor - brain development, brain plasticity, and neural regeneration and repair fields).

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Podcast Guest: Dr. David Linden, Ph.D., Professor of Neuroscience at Johns Hopkins University School of Medicine and the author of many popular books about the brain.)

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Key takeaways

Kraus corpuscles play a crucial role in sensory skills, influencing sexual experience, aging-related sensitivity changes and tactile perception dynamics (Segment 1).
Monitoring human Kraus corpuscles is challenging due to reliance on animal studies, with alterations from structural changes, experiential factors, and desensitization (Segment 2).
Early-life events challenge genetics: myopia, soldier heat stroke linked to light-triggered changes; mice, and voles show the environment's impact on traits (Segment 4).
Human traits vary in heritability: perfect pitch influenced by genes and instruction, earwax type solely genetic, speech accent environmental, and height affected by genes and nutrition (Segment 6).
Human trait heritability varies widely, assessed via twin studies, revealing genetics' role alongside environmental factors and stochastic processes in shaping traits (Segment 7).
Traditionally tied to motor coordination, the cerebellum's wider functions include predicting the future, impacting behaviors, influencing cognitive functions, and social interactions (Segment 10).
Acknowledge the mind-body connection scientifically, considering reciprocal mental-physiological influence; signal transmission via introspection, immunological cytokines, offering insight for advancement (Segment 12).
Neuroplasticity-brain adaptability to experiences is vital for treating neuropsychiatric disorders; neuron connections, inflammation, microglia's role, and exercise benefit mental health and cognition (Segment 14).
Amid COVID-19, Dr. Linden's dyspnea led to an atrial fibrillation diagnosis, revealing a rare synovial sarcoma, defying prognosis uncertainty Segment 18).

Summary

This episode features Dr. David Linden, a distinguished neuroscience professor at Johns Hopkins University School of Medicine, who holds a Ph.D. and has authored numerous widely-read books on the brain. The speakers engage in a discourse regarding the variations observed across individuals, with a particular emphasis on disparities in sensory perception and the influence of chance, heredity, and life events, including prenatal factors, in shaping our physiological and cognitive characteristics. The speakers also examine the reciprocal relationship between the mind and body, as well as the influence of cognitive processes and mental techniques such as meditation and breathwork on our overall well-being. The authors additionally examine the correlation between inflammation and depression. Additionally, they engage in a discussion regarding Dr. Linden's diagnosis of a terminal illness, his psychological state while undergoing chemotherapy, and the insights he has gained from his diagnosis about the cognitive processes of the mind, the concept of thankfulness, the perception of time, and the nature of existence. This episode additionally explores the topics of sensuous touch, cerebellar function, and epigenetic inheritance, making it relevant to anybody with an interest in the fields of neuroscience, genetics, psychology, and human development.

1. 00:07:54 Sensory Touch & Genitals, Krause Corpuscles

Recent research articles have shed light on the perplexing phenomenon surrounding the increased sensitivity and arousal of particular anatomical parts, particularly the genitalia. The recognition of sexual stimulation occurring through various anatomical locations has been acknowledged for a significant duration. Nevertheless, the exact underlying factor contributing to the heightened sensitivity of the vaginal area is incompletely comprehended.

Historical Overview:

The historical origins of the inquiry can be traced back to the year 1860, when Krauss, a German neuroanatomist, made a noteworthy finding. Krauss discovered discrete nerve endings located within the penis and clitoris, thereafter recognized as Kraus corpuscles in contemporary literature (1). Initially, it was assumed that the existence of these nerve endings was linked to sexual feelings. Nevertheless, the occurrence of these structures in other anatomical locations, such as the nipples, lips, and anus, has raised questions over their sole association with sexual stimulation.

Key Experiments:

The conundrum under investigation has been the subject of a recent pre-print study led by David Ginty and his research team at Harvard University, resulting in notable progress in understanding this phenomenon. In this study, researchers used mice as the experimental cohort to investigate, document, and manipulate Kraus corpuscles to gain a deeper understanding of their functional importance. The study's findings suggest that these nerve terminals exhibit mechanical sensory skills, which aligns with their potential involvement in sexual sensation. Furthermore, the research team demonstrated that the utilization of genetic techniques and blue light stimulation to activate these nerve endings led to observable physiological responses, especially the initiation of erections in male mice (2). After the neural receptors in male mice were deactivated, their preference for receptive females remained, while their involvement in mounting, thrusting, and ejaculatory actions decreased. Similarly, the deactivation of these brain synapses in female mice during their estrous phase led to a decrease in their inclination and preparedness to engage in sexual relations. The research stated above provides persuasive evidence for the substantial role played by Kraus corpuscles in sexual experience and behavior (3).

The implications of this disclosure have far-reaching consequences. This phenomenon possesses the capacity to clarify the wide array of individual variations in sexual preferences and experiences, while concurrently offering insights into the changes in sexual sensitivity that transpire as individuals age. The decline of tactile sensitivity in the fingertips as people age is analogous to the probable decrease of Kraus corpuscles in the vaginal region, which may contribute to the reduced sexual sensation observed during the aging process. This study introduces new avenues for further exploration in the domain of sexual experience and tactile perception, generating considerable interest and enthusiasm among scholars. The findings of this study not only offer valuable insights into a long-standing topic but also establish a basis for future research on the intricate dynamics of human sexual encounters. This notable progress underscores the importance of understanding the complexities of tactile perception and its influence on human existence.

Figure 1. Four of the primary mechanoreceptors in human skin, Merkel’s disks, Meissner’s corpuscles, Ruffini endings, Pacinian corpuscles, and Krause end bulbs (3).

References:

Qi, L., Iskols, M., Handler, A., & Ginty, D. D. (2023). Krause corpuscles of the genitalia are vibrotactile sensors required for normal sexual behavior. bioRxiv, 2023-06.
WOLTER, J. R. (1964). Double nerve supply of Krause corpuscles at the human corneal limbus. Archives of Ophthalmology, 71(3), 409-411.
https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/36%3A_Sensory_Systems/36.03%3A_Somatosensation_-_Somatosensory_Receptors

2. 00:16:46 Sexual Experiences & Sensation

The technological challenge of monitoring Kraus corpuscles in humans arises from the necessity of obtaining cadaver tissue, thereby necessitating the reliance on animal studies. Potential explanations for the observed alterations in Kraus corpuscles encompass the concept of structural plasticity, wherein their morphology, dimensions, or concentration may undergo modifications in response to experiential factors. On the other hand, desensitization may manifest as a phenomenon in which extended stimulation results in a transient decrease in sensitivity within the aforementioned nerve terminals. For instance, it has been seen that 3. , potentially as a result of functional alterations rather than discernible structural adaptations in Kraus corpuscles (4). This observation underscores the want for additional investigation to comprehensively comprehend the fundamental mechanisms that propel these alterations.

References:

Meissner, V. H., Dumler, S., Kron, M., Schiele, S., Goethe, V. E., Bannowsky, A., ... & Herkommer, K. (2020). Association between masturbation and functional outcome in the postoperative course after nerve-sparing radical prostatectomy. Translational andrology and urology, 9(3), 1286.

3. 00:19:14 Human Individuality & Variation; Senses & Odor Detection

The podcast featuring Dr. David Linden delves into the challenges of the replication of human experiences in animal subjects. Researchers frequently utilize genetically similar, inbred mice that are raised in controlled environments. The results obtained from enrichment studies, such as the utilization of running wheels, indicate that mice experience improved welfare when allowed to engage in physical exercise. Understanding individual differences is crucial when examining human experiences and evolutionary dynamics. The olfactory system, in conjunction with other sense systems, exhibits significant degrees of individual variability. The olfactory system in humans consists of over 400 odor receptors, and the examination of genomic sequences has revealed significant variation in the genes that encode these receptors among different individuals. Variations in olfactory perception involve the diverse interpretations of specific odors, such as androstenone, which induces pleasurable sensations in certain persons while being considered unpleasant by others. The cultural milieu has a considerable impact on the perception of odors, since individuals may demonstrate suggestibility in their efforts to discern various odors. The presence of variations in olfactory perception among individuals and cultures has substantial implications in terms of both cultural and evolutionary contexts. The reason for this phenomenon might be attributed to the diverse range of habitats inhabited by humans, as well as their changing nutritional preferences, necessitating an adaptive olfactory system.

The human olfactory system. The odorant receptors are localized on olfactory sensory neurons, which occupy a small area in the upper part of the nasal epithelium. Every olfactory receptor cell expresses only one odorant receptor. On activation, signals from olfactory receptor cells are relayed in the glomeruli—well defined micro-regions in the olfactory bulb. Receptor cells of the same type are randomly distributed in the nasal mucosa but converge on the same glomerulus. In the glomerulus, the receptor nerve endings excite mitral cells that forward the signal to higher regions of the brain. Credit: Karolinska Institutet and Nobel Foundation, Stockholm, Sweden.

Figure 2. The human olfactory system. The odorant receptors are localized on olfactory sensory neurons, which occupy a small area in the upper part of the nasal epithelium

References:

5. Niimura, Y. (2012). Olfactory receptor multigene family in vertebrates: from the viewpoint of evolutionary genomics. Current genomics, 13(2), 103-114.

4. 00:31:22 Visual Individuality; Heat Tolerance; Early Life Experiences & Variation

The influence of early life events on specific characteristics presents a challenge to the traditional concept of genetic determinism. The incidence of myopia in children may be impacted by the level of light exposure during the first five years of life. The activation of trophic factors induced by light exposure leads to alterations in the morphology of the eyeball. During World War II, it was observed that soldiers originating from colder regions had a greater frequency of heat stroke incidents. This phenomenon can be related to modifications in the patterns of innervation of sweat glands. The rapid adjustment witnessed within a single generation highlights the advantages of traits shaped by early-life experiences (6). Field mice and voles have similar results, as changes in light exposure during pregnancy affect the fur density of newborns, hence adhering to anticipated temperature conditions. The aforementioned examples highlight the importance of considering environmental factors in shaping features and challenge the assumption that genetic factors alone determine various characteristics.

References:

6. Bick, J., & Nelson, C. A. (2016). Early adverse experiences and the developing brain. Neuropsychopharmacology, 41(1), 177-196.

5. 00:40:28 Auditory Variability, Perfect Pitch

The possession of perfect pitch, which entails the capacity to identify and label musical notes without any external cues, is a relatively uncommon characteristic. Even within the cohort of musicians who have had extensive training, the possession of this particular attribute is seen in just approximately 10% of individuals. The heredity of perfect pitch, as indicated by twin studies, has a moderate level of effect, estimated to be approximately 30-40% (7). However, an interesting observation has emerged, suggesting that early life experiences might exert a substantial impact on the development of perfect pitch. For example, the acquisition of ear instruction at an early stage can significantly augment the probability of cultivating absolute pitch. Although this characteristic is uncommon, its potential for modification through training highlights the interplay between genetic predisposition and environmental influences in the development of distinct skills.

References:

7. Drayna, D., Manichaikul, A., Lange, M. D., Snieder, H., & Spector, T. (2001). Genetic correlates of musical pitch recognition in humans. Science, 291(5510), 1969-1972.

6. 00:42:08 Heritability & Human Individuality: Cognitive & Physical Traits

Human characteristics display varying degrees of heritability, spanning the spectrum from complete genetic determination to complete reliance on environmental influences. Several examples serve to highlight this spectrum. The trait of perfect pitch, which entails the capacity to identify musical notes, exhibits a modest level of heritability. However, the acquisition of this ability can be shaped by early life instruction. The kind of earwax, which is influenced by the abcc11 gene, exhibits 100% heritability. However, it is noteworthy that this gene exerts its influence on other physiological processes beyond earwax production. In contrast, speech accent is solely determined by early-life exposure to speech patterns, without any discernible genetic influence.

The characteristic of height exhibits a substantial hereditary element, estimated to be approximately 85% in the context of the United States. Nonetheless, the degree of heritability diminishes in regions characterized by inadequate nutrition and prevalent infectious diseases, since environmental variables impede the realization of genetic potential. This concept can be applied to the domain of intelligence (8). IQ test scores are subject to the influence of hereditary characteristics as well as environmental settings, including elements such as nutrition, education, and healthcare accessibility. In places characterized by affluence, it has been observed that IQ scores exhibit a heritability estimate of approximately 60-70%. Conversely, in communities facing disadvantages, the heritability of IQ scores tends to decrease as a result of the influence of insufficient resources on the expression of hereditary traits. Fundamentally, although genetics are a prominent determinant of phenotypes, environmental influences also wield considerable sway (9). Ensuring equitable access to fundamental resources and opportunities is crucial in enabling individuals to fulfill their innate potential and cultivate favorable attributes.

Figure 3. A model of human information processing was developed together with Dr. Lennart Schalk (10).

References:

8. https://en.wikipedia.org/wiki/Height_and_intelligence

9. Mottus, R., Marioni, R., & Deary, I. J. (2017). Markers of psychological differences and social and health inequalities: Possible genetic and phenotypic overlaps. Journal of Personality, 85(1), 104-117.

10. Stern, E. (2017). Individual differences in the learning potential of human beings. npj Science of Learning, 2(1), 2.

7. 00:49:36 Heritability, Environment, Personality; Twin Studies

The heritability of human traits has a wide range, necessitating a comprehensive understanding of their origins. Traits can demonstrate varying degrees of heredity, and environmental dependency, or fall along a spectrum encompassing both extremes. The use of identical twins and fraternal twins is commonly utilized in the assessment of heredity. Nevertheless, it is crucial to recognize that specific assumptions, such as the equal environment assumption, can exert an impact on the results derived from these methodologies. Twin studies have provided insights into the heritability levels of various characteristics, including perfect pitch, speech accent, and personality qualities such as Openness, Conscientiousness, Empathy, Agreeableness, and Neuroticism.

Minnesota Study of Twins Reared Apart (MISTRA)

The Minnesota Study of Twins Reared Apart (MISTRA) is a noteworthy inquiry in the realm of heritability evaluation, as it illustrates that, even when genetic factors are taken into account, the impact of familial environments on the formation of personality traits is practically negligible. Several factors, including diet, access to education, healthcare, and random developmental processes, have a substantial part in contributing to variability. The heritability of height demonstrates variability among affluent regions and disadvantaged areas due to differing levels of access to resources. The operation of the genome does not conform to a deterministic blueprint but instead imparts general instructions that lead to stochastic brain development. The manifestation of differences in physical features, behavioral patterns, and brain connectivity in identical twins underscores the impact of stochastic mechanisms during the developing process (12). The nine-banded armadillo, recognized for its capacity to generate genetically identical quadruplets, is frequently utilized as a study model to explore stochastic differences in development. These discoveries underscore the intricate interplay between genetic inheritance, environmental variables, and stochastic elements in shaping human traits.

Figure 4. Diagram of the two paths used to arrive at conclusions in favor of genetics (13).

References:

11. Polderman, T. J., Benyamin, B., De Leeuw, C. A., Sullivan, P. F., Van Bochoven, A., Visscher, P. M., & Posthuma, D. (2015). Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nature genetics, 47(7), 702-709.

12. Grigorenko, E. L. (2000). Heritability and intelligence. Handbook of intelligence, 53-91.

13. Joseph, J. (2022). A reevaluation of the 1990 “Minnesota Study of Twins Reared Apart” IQ study. Human Development, 66(1), 48-65.

8. 01:01:19 Development, Chance; Transgenerational Epigenetic Inheritance

Genetic variety constitutes a substantial determinant of individuality, although additional factors are equally influential in this regard. The formative experiences of an individual's early life, coupled with the inherent randomness in the process of development, have the potential to influence the development of various features. The presence of randomness during the process of development might give rise to phenotypic variants that are not heritably transmitted through genetic means. The concept of transgenerational epigenetic inheritance, which posits the transmission of features between generations without alterations to the DNA sequence, has been suggested but remains mainly unsupported by compelling evidence in mammalian species (14). Various statements have been put forth, frequently based on epidemiological research. However, the credibility of these claims is undermined by methodological concerns such as post hoc hypothesizing and inadequate use of statistical adjustments. Although potential future investigations may elucidate the underlying processes of transgenerational inheritance, it is already evident that the transmission of trauma is predominantly influenced by social factors rather than DNA alterations.

Figure 5. Mechanisms of transfer of information about the ancestral environment or physiology over generations.

References:

14. Zwir, I., Arnedo, J., Del-Val, C., Pulkki-Råback, L., Konte, B., Yang, S. S., ... & Cloninger, C. R. (2020). Uncovering the complex genetics of human character. Molecular psychiatry, 25(10), 2295-2312.

15. Perez, M. F., & Lehner, B. (2019). Intergenerational and transgenerational epigenetic inheritance in animals. Nature cell biology, 21(2), 143-151.

9. 01:07:37 Single Generation Epigenetic Inheritance & Stress; Autism

The influence of epigenetic influences on features within a single generation can be attributed to prenatal experiences. During the 1918 flu pandemic, it was seen that maternal stress had a significant impact on offspring, resulting in various statistical anomalies such as reduced height, elevated incidence of schizophrenia, and probable indications of autism. The potential influence of stress on the developing fetus at a particular stage of development appears to be associated with an immune-neural connection, maybe involving the cytokine interleukin 17 (16). The notion is substantiated by a study conducted by Gloria Choi at MIT, which utilized a mouse model. This study illustrates that immunological signaling molecules have the ability to traverse the placenta and interfere with the formation of the cortex, leading to abnormal cell layering that bears resemblance to the brains of individuals with autism. The precise mechanisms behind autism are still under investigation. Although certain behaviors observed in mice may bear a resemblance to certain elements of autism in humans, the translation of these discoveries to human knowledge is a complicated endeavor.

Figure 6. Several prenatal factors could lead to epigenetic dysregulation in ASD (17).

References:

16. The Effect of In-Utero Conditions on Long Term Health: Evidence from the 1918 Spanish Flu Pandemic.

17. Forsberg, S. L., Ilieva, M., & Maria Michel, T. (2018). Epigenetics and cerebral organoids: promising directions in autism spectrum disorders. Translational psychiatry, 8(1), 14.

10. 01:15:52 Sleep Paralysis; Cerebellum, Prediction

The cerebellum, traditionally recognized for its involvement in motor coordination, possesses a wider range of functions that encompass the ability to anticipate and forecast the immediate future in order to facilitate behavioral regulation. Although historically associated with motor control and coordination, recent research has revealed its intricate associations with brain regions implicated in planning, decision-making, personality traits, and various other cognitive functions (19). The observed augmentation of functions implies that the cerebellum's predictive network exerts an influence on many behavioral domains, encompassing social interactions and the evaluation of affiliative or antagonistic circumstances. The core computational function of the cerebellum, which involves prediction, seems to have undergone evolutionary changes, expanding its scope from motor control to include several other activities.

Figure 7. Hematic brain images showing increased and decreased activity of different brain areas during sleep (19)

References:

18. Šimić, G., Tkalčić, M., Vukić, V., Mulc, D., Španić, E., Šagud, M., ... & R. Hof, P. (2021). Understanding emotions: Origins and roles of the amygdala. Biomolecules, 11(6), 823.

19. Mutz, J., & Javadi, A. H. (2017). Exploring the neural correlates of dream phenomenology and altered states of consciousness during sleep. Neuroscience of Consciousness, 3 (1).

11. 01:23:47 Nature vs. Nature, Experience; Linden Hypothesis

According to Dr. David Linden, the dichotomy of "nature versus nurture" has certain challenges due to its tendency to provide a simplistic viewpoint about the complex interaction between genetics and experiences in the formation of individuals. The author suggests expanding the notion of "nurture" to encompass a wider array of experiences, encompassing not only social factors but also encompassing prenatal development and extending over an individual's entire lifespan. The author emphasizes the complex interaction between genetics and experience, illustrating how these elements can either contradict or complement each other (20). For instance, certain genetic characteristics demonstrate significance solely when they are stimulated by particular experiences, whereas in other cases, genetic predispositions may influence the manner in which experiences are encountered. The relationship in question can be described as a multifaceted interaction between genetic factors and environmental influences, which is further shaped by the random nature of developmental processes.

References:

20. Tsuang, M. T., Bar, J. L., Stone, W. S., & Faraone, S. V. (2004). Gene-environment interactions in mental disorders. World psychiatry, 3(2), 73.

12. 01:30:37 Mind-Body Interaction; Chemical Signals

It is imperative to comprehend the correlation between the mind and body, with particular emphasis on the necessity of adopting a scientific approach rather than a mystical one when examining ideas such as the potential influence of meditation on chronic pain. This entails acknowledging the reciprocal relationship between mental states and the physiological aspects of the body. The concept of "Mind Body" pertains to the reciprocal relationship between mental processes and bodily manifestations, whereby mental activities have an influence on the body, and physiological phenomena in turn impact the mind (21). There are two primary mechanisms via which signal transmission takes place: introspection, whereby neurons examine the internal activities of the body, and the diffusion of immunological signals, such as cytokines, which interact with the neurological system to induce alterations in mental function. The potential for significant advancements in comprehending the complex interplay between the mind and body lies in the investigation of immune signaling molecules, specifically cytokines (21).

Figure 8. Neural circuit that drives physical responses to emotional stress (22).

References:

21. Ogden, P., Minton, K., & Pain, C. (2006). Trauma and the body: A sensorimotor approach to psychotherapy (norton series on interpersonal neurobiology). WW Norton & Company.

22. https://www.eurekalert.org/multimedia/695366

13. 01:39:10 Inflammation & Depression

The research on the correlation between physical inflammation and depression is presently a topic of continuous scholarly inquiry. There exists a widely held idea that the correlation between inflammation and depression can be explained by two main mechanisms: firstly, the transmission of signals to the brain through neurons that detect inflammation, and secondly, the impact of immune signaling molecules, such as cytokines, on mental functioning. Depression is characterized by a wide range of biochemical abnormalities rather than being a distinct condition (23). The correlation between inflammation and depression has been established; yet, the effectiveness of direct therapies, such as the utilization of anti-inflammatory drugs, has not consistently shown beneficial results. However, there is research that focuses on particular cohorts of individuals, particularly those who do not show positive reactions to traditional antidepressant treatments. This research suggests that anti-inflammatory drugs could offer potential relief. This observation highlights the complex relationship between inflammation and depression, suggesting promising developments in the field of mind-body medicine.

Figure 9. Hypothetical model of bidirectional interactions between systemic low-grade inflammation and depression (24).

References:

23. Slavich, G. M., & Irwin, M. R. (2014). From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychological bulletin, 140(3), 774.

24. Suneson, K., Lindahl, J., Chamli Hårsmar, S., Söderberg, G., & Lindqvist, D. (2021). Inflammatory depression—mechanisms and non-pharmacological interventions. International journal of molecular sciences, 22(4), 1640.

14. 01:43:35 Neuroplasticity, Inflammation & Mental Disorders; Microglial Cells, Exercise

Neuroplasticity, a phenomenon denoting the brain's ability to alter its structure and function in response to diverse experiences, holds significant importance in the management and treatment of neuropsychiatric illnesses. The phenomena refer to changes in the connections between neurons, adjustments in the structure of brain circuits, and the interaction between inflammation and synaptic plasticity. Non-neuronal cells present in the brain, such as microglial cells, play an active role in this specific physiological process. These entities have the capacity to modify the extracellular environment, influence synaptic plasticity, and demonstrate sensitivity to inflammatory stimuli. Research has demonstrated that physical exercise exerts significant effects on mental and cognitive well-being, primarily by engaging several biological systems that directly involve microglial cells, neurons, and the brain's vasculature. Research studies have demonstrated that engaging in regular physical exercise has the potential to augment cerebral blood flow, maintain the elasticity of blood vessels, and function as a protective measure against cognitive decline and feelings of depression associated with aging (25). This discovery highlights the interconnectedness of physical activity, brain health, and mental well-being.

Figure 10. Summary of the review. (1) We listed animal and clinical experiments on the intervention of aerobic PE in brain dysfunction and concluded that aerobic PE can improve cognition, fight depression, and relieve chronic pain. (2) Aerobic PE interferes with brain disorder through four common mechanisms: anti-inflammatory mechanisms, synaptic plasticity, hippocampal atrophy, and hippocampal neuronal apoptosis. (3) We propose the hypothesis that aerobic PE interferes with brain disease through the bone-brain axis.

References:

25. Kennedy, G., Hardman, R. J., Macpherson, H., Scholey, A. B., & Pipingas, A. (2017). How does exercise reduce the rate of age-associated cognitive decline? A review of potential mechanisms. Journal of alzheimer's disease, 55(1), 1-18.

26. Jia, Y., Yao, Y., Zhuo, L., Chen, X., Yan, C., Ji, Y., ... & Zhu, Y. (2022). Aerobic Physical Exercise as a Non-medical Intervention for Brain Dysfunction: State of the Art and Beyond. Frontiers in Neurology, 13, 862078.

15. 01:52:15 Fads & Science

In a podcast, Dr. David Linden highlights that scientists, despite their commitment to logic, can be prone to adopting trends and fads. Throughout the passage of time, numerous study fields and approaches have received considerable attention and reputation within the scientific community. The 1980s had a notable focus on opioid peptides, followed by a second period centered on gaseous neurotransmitters like nitric oxide. Currently, glial cells have attracted considerable scholarly interest, and while this attention is well-founded, there is discernible evidence of the emergence of patterns and the embrace of prevailing viewpoints. The occurrence of trend-following is evident not only in the choice of research topics, but also in the utilization of research methodology. One illustrative instance is the method of single-cell expression profiling, wherein the examination of gene activity is conducted at the level of individual cells (27). This technique holds considerable usefulness; nevertheless, it also carries the risk of being excessively employed. Upon reflection, it is conceivable that forthcoming scientists may deliberate about the potential excessive emphasis placed on single-cell profiling throughout the current era of 2023.

References:

27. O’Sullivan, S. J., Malahias, E., Park, J., Srivastava, A., Reyes, B. A., Gorky, J., ... & Schwaber, J. S. (2019). Single-cell glia and neuron gene expression in the central amygdala in opioid withdrawal suggests inflammation with correlated gut dysbiosis. Frontiers in Neuroscience, 13, 665.

16. 01:55:16 Mind-Body Communication; Cancer

Bidirectional connection between the human body and the brain is facilitated by two separate channels, enabling the transfer of impulses. One component is the propagation of brain signals along neuronal pathways, as well as the participation of hormones, neurotransmitters, and cytokines. Within the realm of oncology, there exists a noteworthy phenomenon wherein melanomas that are innervated demonstrate a less favorable prognosis. Neurons possess the ability to secrete signaling chemicals, including calcitonin gene-related peptide (CGRP), which has been reported to impact the immune surveillance process in the vicinity of tumors (28). This suggests that the activity of neurons has the capacity to influence the advancement of cancer. As a result, it can be hypothesized that cognitive activities, such as meditation, may have the capacity to impact the progression of cancer through the interrelated pathways involving the brain, neurons, and tumors. While this hypothesis is hypothetical in nature, it underscores the potential for additional investigation into mind-body signaling, which has been relatively understudied thus far.

Figure 11. Biological Mechanisms of MBT (29).

References:

28. Balood, M., Ahmadi, M., Eichwald, T., Ahmadi, A., Majdoubi, A., Roversi, K., ... & Talbot, S. (2022). Nociceptor neurons affect cancer immunosurveillance. Nature, 611(7935), 405-412.

29. https://positivepsychology.com/mind-body-connection/

17. 02:03:28 Mind-Body, Mediation, Breathwork

Biomedical researchers have the responsibility of distinguishing between scientifically valid statements and unsupported ideas lacking a biological basis. The objective at hand entails undertaking comprehensive investigations into multiple hypotheses, including those positing a relationship between cognitive processes and physiological functions (30). While some comparisons can be based on valid biological concepts, others are merely speculative or lack empirical evidence. The primary goal is to conduct a thorough analysis and understanding of the fundamental mechanisms that govern these connections, with the intention of optimizing their potential impact. The undeniable influence of mental processes on the physiological state of the body is exemplified by the observed association between sleep deprivation and the occurrence of sepsis. Breathwork, as an illustrative example, demonstrates promise in revealing different patterns of brain activity that align with respiratory rhythms. The main duty of the scientific community is to differentiate between substantiated claims and unsubstantiated ideas, as well as to clarify the genuine underlying biological mechanisms.

References:

30. Roberts, R. E., & Duong, H. T. (2014). The prospective association between sleep deprivation and depression among adolescents. Sleep, 37(2), 239-244.

18. 02:07:30 Atrial Fibrillation, Synovial Sarcoma, Heart

During the summer of 2020, amidst the COVID-19 pandemic, Dr. David Linden encountered a significant manifestation of dyspnea, prompting him to consider a potential association with COVID-19. Despite undergoing many negative tests, his symptoms continued to linger. Upon seeking medical assistance, the individual received a diagnosis of atrial fibrillation, a medical disease characterized by abnormal heart rhythms (31). Following medical intervention, an echocardiography was conducted and identified the presence of a mass exerting pressure on the individual's heart. Subsequent analysis determined the mass to be a teratoma, a congenital abnormality characterized by the presence of diverse cell types. Subsequent examination revealed that the malignancy in question was synovial sarcoma, an infrequent form of cancer. The neoplastic condition necessitated the performance of a cardiac surgical procedure involving the opening of the heart, which presented a higher level of complexity than initially anticipated. Despite the infrequency of synovial sarcoma occurrence in the cardiac region and the scarcity of accessible medical data, Dr. Linden's original prognosis was pessimistic, with an estimated life expectancy of 6 to 18 months. The author notes the difficulties that oncologists encounter when providing estimates of lifetime, given the constraints of limited information. Furthermore, the author emphasizes the inherent uncertainty associated with making such forecasts. Currently, Dr. Linden has exceeded the first estimation and underscores the intricacy involved in formulating precise prognoses for exceptional circumstances such as his own.

Figure 12. Atrial Fibrillation Pathophysiology: Normal conduction is affected in atrial fibrillation where multiple disorganized atrial impulses may be sent to the AV node (31).

References:

31. Mitrani, R. D., Dabas, N., Alfadhli, J., Lowery, M. H., Best, T. M., Hare, J. M., ... & Goldberger, J. J. (2022). Long-term cardiac surveillance and outcomes of COVID-19 patients. Trends in cardiovascular medicine, 32(8), 465-475.

31. https://www.ezmedlearning.com/blog/atrial-fibrillation-symptoms-ecg-causes-treatment

19. 02:14:22 Gratitude & Anger; Chemotherapy, Curiosity & Time Perception

Dr. David Linden, who was diagnosed with cardiac malignancy, through a complex array of emotional responses, encompassing sentiments of both rage and appreciation. In spite of his intense emotional state, he harbored profound gratitude for his existence. The individual came to an understanding of the intricate cohabitation of divergent emotions, wherein the experience of being both appreciative and indignant was acknowledged. The inquisitive and intellectually inclined disposition of Dr. Linden had a pivotal role in driving his actions and shaping his medical trajectory, as his cognitive faculties exerted a significant impact on his overall journey. Throughout the course of chemotherapy, the individual encountered difficulties in sustaining a good emotional disposition. However, they adopted an analytical approach to observing their emotional reactions, so enabling them to exert influence over their cognitive state. The individual's encounter further underscored the inherent flexibility of perception, particularly in the context of temporal perception (32). The manner in which information is delivered can have a profound impact on an individual's viewpoint and affective reaction. The pivotal role played by Dr. Linden's intellectual curiosity, self-reflective nature, and comprehension of the intricate relationship between emotions and perception was crucial in shaping his experience during the process of cancer diagnosis and subsequent treatment.

References:

32. Tu, L., Lv, X., Yuan, C., Zhang, M., Fan, Z., Xu, X., ... & Wang, H. (2020). Trajectories of cognitive function and their determinants in older people: 12 years of follow-up in the Chinese longitudinal healthy longevity survey. International Psychogeriatrics, 32(6), 765-775.

20. 02:19:58 Death, Brain & Future Prediction, Religion & Afterlife

Dr. David Linden, a cancer patient, acknowledges his inability to fully immerse himself in the concept of his own mortality. This is a fundamental characteristic of all humans, and the brain's ongoing subconscious anticipation of future events is attributed to this. The brain's tendency to anticipate the immediate future inevitably presupposes one's presence in that future (33). This observation is linked to the widespread existence of religious ideologies throughout societies and historical periods, which often include notions of a hereafter or reincarnation. Dr. Linden believes these beliefs may originate from the brain's inherent tendency to make predictions, causing individuals to construct narratives about a persistent awareness despite their limited capacity to see a world devoid of their existence (33). His personal experience with illness has led him to reflect on the complex interplay between the brain's predictive functions, human perceptions of the afterlife, and the universal human endeavor to comprehend the notion of death.

Figure 13. Timeline of historical events related to brain death and organ donation after brain death and circulatory death (Not directly related but for people who are more interested) (34).

References:

33. https://www.pewresearch.org/2008/05/05/what-brain-science-tells-us-about-religious-belief/

34. Kondziella, D. (2020). The neurology of death and the dying brain: A pictorial essay. Frontiers in Neurology, 11, 736.

21. 02:24:15 Life Advice; Time Perception & Gratitude

In his analysis, Dr. David Linden reflects upon his personal perception of time following his cancer diagnosis, noting that the duration seems to have elongated due to the emotionally significant events that have unfolded over this interval. The individual discusses the act of participating in deep conversations with close associates, increasing the frequency of journeys, and perceiving a sense of acceleration in their activities, all of which have the potential to influence their perception of time. However, it is important to note that his expression of gratitude does not center around little concerns, but instead emphasizes the most essential aspects of human existence.

Linden's Opinion

As per Dr. Linden's perspective, the notion of appreciation revolves around the condition of being a self-aware human and the opportunity to own a life that facilitates engagement in intellectual endeavors and the manifestation of creative creativity. In addition, the person expresses deep appreciation for the significant love and care given to him by his spouse and children. The person recognizes their want to prolong their lives; nonetheless, it is the thought of separating from their cherished companions that evokes the most profound anguish (35). While the individual acknowledges the value of personal experiences, their primary focus lies in the formation of connections and relationships, which they consider to be of utmost importance.

Figure 14. Gratitude and well-being (35).

References:

35. https://www.nia.nih.gov/health/providing-comfort-end-life

36. https://www.futurelearn.com/info/blog/gratitude-and-happiness-importance-being-grateful

Preprint

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Dr. David Linden: Life, Death & the Neuroscience of Your Unique Experience