Friday, September 16, 2016

PLEASURE AND REWARD: WANTING, LIKING, AND HEDONIC HOTSPOTS

Vincent P. de Luise MD


What is pleasure?   

Pleasure can mean different things to each of us. For some it might be doing a sport, while for others it could be practicing yoga, eating ice cream, meditating,  sailing  a boat, love-making, having a religious experience,  or simply lying on a beach. The ancient Greeks talked of happiness as being a combination of hedonia (pleasure) and eudaimonia (well-being and human flourishing by doing "good work" for others).

Certain pleasures have been studied neurologically, using a non-invasive brain scan called functional magnetic resonance imaging, or fMRI. An fMRI scan tracks changes in blood flow (hemoglobin) to various brain regions as a result of a specific stimulus. The more hemoglobin (therefore, the more oxygen) to a specific brain site, the more activity. 


A significant body of scientific research has been published evaluating brain responses to four specific pleasurable stimuli: eating chocolate, listening to music that causes “frissons" (those thrilling “goosebumps” and “chills up or down the spine”  that one gets to particularly pleasurable music), sexual climax,  and,  for those who unfortunately have a need for them, taking addictive drugs, i.e., drugs like cocaine and heroin, which stimulate the brain’s so-called mu-opioid and cannabinoid systems.   

All four of these distinct, pleasure-inducing stimuli (chocolate, music, orgasm, addictive drugs) activate the same brain areas, anatomically adjacent to each other in a region called the medial forebrain (MFB). These areas are:  1) the ventral tegmental area (VTA) ( specifically a little blob of neurons in the VTA called the nucleus accumbens); 2) the prefrontal cortex; 3) the anterior cingulate cortex (especially its subgenual area, above the nucelus accumbens (not shown));  and 4)  the amygdala.  

Axial transection of human brain       from Harley.com


Pleasure, Reward and the "Happiness Trifecta"
 
These four brain areas are part of what cognitive neuroscientists describe as the Reward-Pleasure System. What we feel as desire and pleasure occurs in this system, which is also sometimes referred to as the Wanting/Liking System. This system tells the memory centers in the brain to pay attention to everything associated with that experience, so it can be repeated in the future. The Reward-Pleasure System is activated and controlled by molecular neurochemicals called neurotransmitters, specifically dopamine, serotonin, and oxytocin. 

Evolutionarily, the Reward System is an ancient pathway: the use of dopamine neurons to interconnect behavioral responses to natural rewards has been observed in various species of worms and flies, whose ancestors were around two billion years ago!

These three neurotransmitters - dopamine, serotonin and oxytocin - mediate every pleasurable moment, including the “giving experience,” so much so that Eva Ritvo M.D., vice-chair of psychiatry at the University of Miami School of Medicine, has termed them the “Happiness Trifecta.” 
 
Dr. Ritvo asserts that "giving is a powerful pathway for creating more personal joy and improving health. Any activity that increased the production of these neurotransmitters will cause a boost in mood and cause happiness." Dopamine is connected to motivation, reward and arousal. Serotonin is connected  to memory, learning, sleep and appetite.  Oxytocin, nicknamed "the cuddle hormone," has a powerful effect on the brain and the body. "When oxytocin begins to flow, blood pressure decreases, bonding increases, social fears are reduced, and trust and empathy are enhanced” Dr. Ritvo explains.
 
Giving to others triggers a release of oxytocin, which boosts mood and counteracts the stress hormone, cortisol. The higher the level of oxytocin, the more one wants to help others, Interestingly, when oxytocin is boosted, so are dopamine and serotonin. According to Dr. Ritvo, "even small repeated boosts of the Happiness Trifecta will produce a benefit. Donating money or time... are wonderful ways to give. When we step outside of ourselves long enough to help someone else, something wonderful is waiting for us when we return: the Happiness Trifecta neurochemicals are all boosted ! "


Nerve-nerve cables, called neural networks, interconnect the pleasure centers. These neural networks work electrically, as well as chemically through the neurotransmitters.  When we experience pleasure, we are, in essence, getting a reward.  

Much of pleasure has to do with what cognitive neuroscientists call the "Wanting/Liking" system in the brain, which is part of the "Reward-Pleasure" circuit.


Hedonic Hotspots, Enkephalins and Anandamides


Things are actually a little more complicated than the Happiness Trifecta of dopmaine, serotonin and oxytocin. University of Michigan researchers Morton Kringelbach, Terry Robinson and Kent Berridge have discovered that there are neurochemical differences in our brains between “wanting” something and “liking” it.

The “Wanting”  or "Desire" part of the system is largely mediated by dopamine, the same neurotransmitter that is involved in drug addiction with cocaine and heroin. Dopamine, according to Berridge, contributes more to motivation ("Wanting") than to the actual sensation of pleasure ("Liking") itself.



The “Liking" (or "Pleasure") system” in the brain is mediated by  neurotransmitters called enkephalins and anandamides. There specific areas in the brain which have dense populations of these neurotransmitters. These areas serve as waystations for "Liking."  Berridge calls these “Liking" system brain areas “hedonic hotspots.”   ("hedonic” means "pleasant" (recall the ancient Greeks, hedonia, and our modern-day notions of hedonism).



The enkephalins bind mostly to what are known as opioid (mu-opioid) receptors in the brain. The anandamides, in contrast, bind to cannabinoid receptors. They are termed cannabinoid because they are similar to receptors which bind the cannabinoids  (molecules which are also contained in marijuana). Yes, we humans make our own opioids and cannabinoids in our brains, in much smaller concentrations than if they are taken externally. Nonetheless, isn't it fascinating that opioids and cannabinoids are endogenously manufactured in our brains !?



Two key hedonic hotspots in the brain are a specific region in the nucleus accumbens called its medial shell, and another area, the ventral pallidum, which is right below the nucleus accumbens (and different from the ventral tegmental area discussed earlier).



A bite of chocolate, for example, prompts neurons in these hedonic hotspot areas to release neurotransmitters in the encephalin family,  which are endogenous opioids that are made in our brains. According to Berridge, these enkephalins then interact with receptor proteins that cause the release of anandamide, our brain’s own home-made version of a marijuana cannabinoid. The anandamide, in turn, can interact with other neuronal receptors, producing more enkephalin and intensifying the pleasurable experience.



Interestingly, these anandamide (cannabinoid) receptors are located much more densely in the cerebral cortex ("the "thinking brain") than in the limbic system of the mid-brain (the "subconscious brain"). 

What does this mean? It means that when we desire, seek, or are motivated for pleasure, we release lots of dopamine to get what we want. When we get what we want ("sex, drugs, rock and roll," and chocolate), we really like it, through the release of enkephalins and anandamides. 




It turns out that, among these stimuli, it is music that is particularly exciting to humans, especially music that causes those "chills" down one's spine, the musical frissons. Music is a powerful stimulus of the brain's pleasure center, activating the same neural network receptorsas do addictive drugs, secual climax and dark chocolate Why would that be?

What is the role of music in human evolution? Are humans hard-wired for music? Music may have a foundational and evolutionarily adaptive role in our brains. 


That is the topic for the next A Musical Vision essay.


@ Vincent P. de Luise MD 2015







Kringelbach, M. and Berridge, K., The Joyful Mind, Scientific American, August 2012.

Friday, December 11, 2015

EUTERPE DECONSTRUCTED: REFLECTIONS ON THE HEALTH, ILNESSES AND LEGACY OF WOLFGANG MOZART

This essay was  published in the  Fall 2015 edition of the Hektoen International Journal of Medical Humanities.

Vincent P. de Luise MD


Wolfgang Mozart, age 26,
by his brother-in-law Joseph Lange (1782-1789).

Who was Mozart?
Of course, we all know his music. The music! That music, so refined and richly textured, melodic, timeless, ineffably beautiful, and sublime.
But, who was Mozart? Who was the man behind those genius creations? So much has been written and said about Johannes Chrysostomus Wolfgangus Theophilus Mozart, true and vetted, and more than a little hyped, hyperbolic, and apocryphal, that the truth has been hidden. There are so many stories circulating about Mozart that they have their own name: “Mozart myths.” Even the observation that posterity calls him "Amadeus"—when that name was not on his birth certificate nor a name that he used in his lifetime—is part of that myth. (N.B.: He preferred Wolfgang Amade’ Mozart).
Who was Mozart? There are many Mozarts. There is the eighteenth century Mozart, the undiscovered and neglected artistic genius. There is the re-imagined nineteenth century Mozart, the perfect, porcelain musical god on a pedestal. Today, there is the deconstructed twenty-first century Mozart, whose 626 canonical compositions are now as commonly heard on historically-informed, performance-pattern instruments (H.I.P.) as they are by full modern orchestras, the Mozart who is recognized today as western music’s “first freelance" musician, a peerless and foundational composer for so many that came after him. For many listeners, one or another of the above historical Mozart remains their truth, regardless of the truth.
Mozart is certainly known by his music, music at once joyous, yet tinged with sadness. Can anything more be revealed by an examination of Mozart, the man? By examining aspects of his physiognomy, his personality, the written evidence of his chronic illnesses, the proximate cause of his death, or by his legacy and his "effect"? Can this exegesis illuminate more of this most wondrous of stars in the musical firmament?
The observations below are gleaned from the written literature and vetted scholarship. They paint a portrait of a man with all the imperfections and warts of humanity, who at the same time possessed a gift so rare and so extraordinary that its output, that music which is so beloved, has been likened to the foundational melodies and rhythms that emanate from the center of the universe.
Mozart by Barbara Kraft, The posthumous oil of 1819 Gesellschaft der Musikfreunde, Wien
What did Mozart look like?
More than any other composer, Mozart's image remains one of the least certain. An influential German biographer of the early twentieth century, Arthur Schurig, asserted that, "Mozart has been the subject of more portraits having no connection with his actual appearance than any other famous man; and there is no famous man of whom a more worshipful posterity has had a more incorrect physical picture than is generally the case with Mozart." Can any painter truly capture genius in a portrait? The answer is self-evident.
There are about fourteen vetted and attested portraits of Mozart. Some of these derive from others, so there are actually about ten distinct visual representations of the composer. He had a strong nose and chin, fine blondish hair, a slight esotropia, bilateral exophthalmos, an anomalous external left pinna (but obviously a pristine inner ear, given his absolute pitch and eidetic memory). The Lange portrait (above) and the Kraft posthumous portrait (for which Kraft used the 1781 dalla Croce Mozart family portrait as a reference) were said by Mozart’s sister Maria Anna (Nannerl) and his wife Constanze Weber Mozart Nissen to be the best likenesses.
Descriptions by Mozart's contemporaries are even more illuminating. Nannerl commented that "my brother was a rather pretty child,” but his looks were permanently disfigured by scars" after a bout of smallpox that both siblings sustained in 1767 (he, age 11; she, age 16). Nannerl went on to describe Mozart in her reminiscences in 1792, a year after his death, as being "small, thin, and pale in color and entirely lacking in any pretensions as to physiognomy and bodily appearance."
Mozart is said to have suffered a temporary "blindness" as a result of the marked inflammation of his eyes (this could have been from a keratitis (a corneal inflammation) secondary to the Vaccinia virus of smallpox) and developed facial scars. Yet, in 1770, three years after that same smallpox epidemic, the composer Johann Adolph Hasse wrote that "the boy Mozart is handsome, vivacious, graceful, and full of good manners."
Michael Kelly, the tenor whose vocal talent was much beloved by Mozart and who sang the roles of both Don Basilio and Don Curzio in the premiere of Le Nozze di Figaro (The Marriage of Figaro), famously reminisced in 1826 about Mozart: "He was a remarkably small man, very thin and pale, with a profusion of fine hair, of which he was rather vain. He always received me with kindness and hospitality. He was fond of punch, of which I have seen him take copious draughts. He was kind-hearted and always ready to oblige; but so very particular that when he played, if the slightest noise were made, he left off."
Thomas Attwood, who was Mozart's composition student between 1785 and 1787, recalled his teacher being "of cheerful habit, though lacking a strong constitution." Attwood also remembered that "in consequence of being so much over the table when composing, he (Mozart) was obliged to have an upright desk and stand when he wrote."
There is evidence that Mozart was small in stature. It has been estimated that he stood about 1.6 meters in height, or five feet, three inches. Mozart himself corroborated this when, as a fourteen-year-old in April 1770, he wrote from Rome to his sister in Salzburg about a visit to St. Peter's Basilica, stating, "I had the honor of kissing St. Peter's foot in the church, and having had the misfortune of being so small, I, that same old dunce Wolfgang Mozart, had to be lifted up."
In 1777, at Mannheim, Mozart first met the Webers, the family of Caecilia and Fridolin, whose four musically talented daughters would figure greatly in his life. Although Mozart later married Constanze Weber, he initially fell in love with her elder sister, Aloysia, who spurned him. In her dotage in the 1830s, Aloysia was asked why she rejected so famous a man as Mozart, to which she replied, "I did not know, you see . . . I only thought . . . well . . . he was such a little man." Mozart himself may have put it best when he stated, "Mozart magnus, corpore parvus" ("Mozart the great, small in size").
What ailed Mozart? His health and illnesses
For someone possessed of such remarkable productivity, Mozart was often quite ill. To be sure, his health was in large part a consequence of his era, a function of the endemic diseases and epidemics to which he was inevitably exposed as a result of extensive travels undertaken in childhood. For example, in the fall 1765, while on the grand tour that included the Hague, first Nannerl then Mozart contracted typhoid fever, and both children almost died. He and Nannerl also contracted what has been clinically described as acute rheumatic fever.
There is a large body of literature regarding Mozart's chronic diseases, much of it conjecture. The following is a partial summary of what Mozart may have contracted during his life, as deduced by a careful reading of the primary medical literature and commentary, in German, of his physicians’ observations, and by the writings of friends and observers: recurrent streptococcal infections, erythema nodosum (a nodular and painful skin disease related to a systemic inflammation), typhus, variola (smallpox), quinsy (tonsillar abscess), recurrent bouts of acute rheumatic fever, and renal (kidney) disease.
The putative recurrent streptococcal illnesses may have led to chronic endocarditis (heart disease) and chronic renal disease, specifically a post-streptococcal glomerulonephritis, which in turn could have led to renal failure. Mozart may also have had antimony over-dosage (he was self-medicating with it), a subdural or extradural hematoma (vide infra), and renal hypertension. There is also the possibility that he had acute trichinosis (Hirschmann Arch Int Med 161:1381-1389, 2001. Indeed, Mozart wrote to Constanze in October 1791 that he had eaten two pork cutlets, “con gusto!”). There is no evidence that Mozart ever took mercury, nor is there any clinical description by his physicians that he had ever contracted syphilis. Indeed, Mozart frequently documented his faithfulness to his wife Constanze and said he would never frequent prostitutes.
Peter G. Davies, M.D., the Melbourne gastroenterologist and Mozart biographer, has posited that Mozart suffered from the manic-depressive disorder cyclothymia (J. Roy. Sc. Med. 1991). The possibility of cyclothymia, quite common in many creative types, would potentially explain some of Mozart's bursts of extraordinarily intense creativity, such as in the summer of 1788, when he wrote the last three symphonies, his greatest in the genre. These works were composed with no known commission and Mozart never heard them performed except in his imagination. On the other hand, such an explanation must be weighed against several periods of sustained productivity, such as the years 1784 to 1786, when Mozart created an extraordinary number of masterworks in every musical genre. Further complicating Davies’s claim is the more recent and close reading of the primary literature, in the original German, by Lucas Karhausen, who compellingly argues against cyclothymia or any mood disorder.
A distinction should be made between Mozart’s chronic illnesses and the proximate causes of his abrupt and early demise. Davies suggests that Mozart died of the consequences of a cerebral hemorrhage resulting from hypertension secondary to an acute nephritis, possibly from Henoch-Schönlein purpura, a rare disease which can result from streptococcal infection. Mozart was likely severely anemic and already in uremic coma. To compound matters, his physician, Dr. Thomas Franz Closset (one of the best in Vienna), bloodlet him of almost a liter of blood, which only served to worsen the anemia and hasten his death. Karhausen agrees with the possibility of an acute infectious illness but does not rule out acute rheumatic fever, which was also the consensus of the 2000 Delphi panel of physicians at the University of Maryland.
Mozart's death certificate (there was no autopsy) stated “hitziges Frieselfieber” (“heated miliary fever”), a common clinical diagnosis of that era, but one which is far too non-specific a term on which to opine a diagnosis. It may relate to the inflammatory rash of rheumatic fever, which in turn may have been a result of Mozart's presumed repeated streptococcal infections. Richard Zegers M.D. (Ann Int. Med. 2009) reviewed the records of 5,011 Viennese adults who died in the two months before and after December 1791, and compared that data to comparable months in 1790 and 1792, finding a much higher than normal rate of death from an epidemic of presumed streptococcal infection in 1791.
In early 1789, and again in 1790, Mozart fell, landing on his left temple, and, as a result, may have sustained a chronic subdural hematoma that also manifested itself as a fracture to his skull (M. Drake, Neurol 1993).
The putative Mozart calvarium in the Mozarteum, Salzburg
There exists a calvarium (a skull that lacks its mandible) in the possession of the Mozarteum in Salzburg, which was exhumed in 1801 by a man named Radschopf, the successor of the grave digger who buried Mozart on December 1791. The condition of the calvarium reflects a trauma like that of a repeated fall and fracture which may be that of Mozart.
However, a forensic examination in 2006, comparing DNA from the calvarial scrapings to the osseous remains of his relatives were inconclusive, largely because none of the DNA matched any of the others. This lack of concurrence may be a result of the gravesites having been disturbed many times over the preceding two hundred years.
Franz Joseph Haydn on Mozart and the author Karoline Pilcher on both
Franz Joseph Haydn recognized Mozart's genius during his lifetime and before most anyone else. Haydn said as much to Mozart’s father, Leopold, at a February 12, 1785 string quartet party at which the last three of Mozart's six string quartets dedicate to Haydn were performed. Haydn said: "I tell you before God, and as an honest man, that your son is the greatest composer known to me in person or by name. He has taste, but above all, he has the greatest knowledge of composition."
After Mozart's death, Haydn wrote to his friend Michael Puchberg in 1792 that "for some time I was quite beside myself over his death, and could not believe that Providence should so quickly have called away an irreplaceable man into the next world.” Haydn went on to write that "posterity will not see another talent as his in a hundred years."
The author Karoline Pilcher was a contemporary of Mozart and Haydn and knew both of them personally. In the 1820s, in her reminiscences, Pilcher writes this about them (translated here from the German):
"Mozart and Haydn, whom I knew well, were men who displayed in their personal intercourse no other outstanding mental ability and almost no sort of intellectual cultivation of a learned or higher education. Everyday character, flat humor and with the first (Mozart) a scantly sensible lifestyle, was all they publicly manifested, and yet, what depths, what worlds of fantasy, harmony, melody and feeling, lay concealed within these modest exteriors! Through what inner revelation came to them this understanding, how they must have seized it, to bring forth such powerful effects, and express in tones, feelings, thoughts, passions, that every ear must feel with them, and be spoken to us as well as from greater depths."
The Mozart effect
Almost as abundant as the varied speculation about Mozart's health, illness, and death, is the literature on the neurological, cognitive, and psychophysiological effect of Mozart's music on the listener. This discussion, originally grounded in rigorous scientific study, has formed the basis of later and popular claims revolving around the so-called “Mozart effect."
The French otolaryngologist Alfred Tomatis coined the term “Mozart effect" in a 1991 book entitled Pourqoui Mozart? about the concept of auditory processing integration. While examining opera singers who were having trouble reaching and singing certain notes in tune, he discovered that those singers all had a coincident hearing defect in the same frequency as the vocal problem.
This relationship between audition (hearing) and phonation (voicing) was first posited by Tomatis, who stated that "the voice can only reproduce what the ear can hear." He subsequently focused his audiological research using Mozart's violin concertos, as well as Gregorian plainchant, at different hearing frequencies, to improve auditory processing. To "retrain the ear," if you will, of patients who had acquired sensori-neural hearing loss. Among those who gained improvement not only in their hearing as well as in their "voicing" by this technique were the actor Gerard Depardieu, the baritone Benjamin Luxon, and the popular singer Sting (Gordon Sumner).
In 1993, Frances Rauscher, Gordon Shaw, and Katherine Ky,  researchers in the department of neurobiology at the University of California, Irvine, further investigated a “Mozart effect" in an experiment which was published in the October 14, 1993 issue of the scholarly scientific journal Nature under the title "Music and Spatial Task Performance."
Rauscher’s team found that a group of students who were "pre-treated" for ten minutes by listening to the first movement and part of the second movement of Mozart's two-piano sonata in D major, K. 448, performed better on a spatial-task reasoning Stanford-Binet test than when the same students were pre-treated with a "relaxation tape" or after they had sat in silence for ten minutes prior to testing. (Stanford-Binet testing is a form of IQ test, which measures aspects of verbal and non-verbal reasoning.) In the Rauscher study, the students were given a paper folding and cutting test: a piece of paper is folded several times and then cut. The students had to mentally "unfold" the paper and choose the correct shape from the numerous examples that they were given. These results were temporary, lasting only through the time taken for the experiment (about fifteen minutes) and were specifically related to visual-spatial task reasoning, and not to other measures of intellect. More recent research has both confirmed and contradicted the results of the Rauscher study, among them "Arousal, Mood, and the Mozart Effect," Psychological Science (2001); "Re-examination of the Effect of Mozart's Music on Spatial Task Performance," Journal of Psychology (1997); "'Brain-Based’ Learning: More Fiction than Fact," American Educator (2006); and "Prelude or Requiem for the Mozart Effect," Nature (1996). The music educator Don Campbell was influenced by Tomatis's work and the results of the Rauscher study and went on to write the best-selling 1997 book The Mozart Effect: Tapping the Power of Music to Heal the Body, Strengthen the Mind, and Unlock the Creative Spirit. Campbell's claims went far beyond spatial intelligence improvement to include notions that Mozart's music improved mental health and cognitive ability. Over the decades, the “Mozart effect,” as put forth in Tomatis's original work and subsequent misinterpretations of the Rauscher study, has devolved into an assertion that early childhood exposure to classical music (specifically, Mozart's music) can ipso facto bestow a beneficial effect on mental development, leading to advantages and a range of lifetime achievement.
However, there a kernel of scientific fact in the studies. There is a feature intrinsic to the music of Mozart (and several other composers) that modifies or enhances brain function (J. Jenkins, Royal Society of Medicine, 2001). Neurologists John Hughes and John Fino subjected to computer analysis eighty-one works by Mozart, sixty-seven of Johann Sebastian Bach, sixty-seven of Johann Christian Bach, and 150 works by fifty-five other composers. These researchers at the University of Illinois found that the music of Mozart as well as that of J. S. and J. C. Bach, but not the music of the other composers, contained a high degree of long-term periodicity. They hypothesized that these specific harmonic patterns and chordal repetitions, found especially in the music of Mozart and J. S. and J. C. Bach (the latter was an influence on the young Mozart) have a function in brain coding: they act to align or "symmetrize" neurons in certain regions of the brain involved with auditory processing and memory (specifically the parietooccipital cortex and right prefrontal cortex) and which can lead to heightened mental capacity and function, even if only temporarily. There is thus neurophysiological evidence for a “Mozart effect" (as well as a "J. C. Bach effect" and a "J. S. Bach effect"). There are fundamental and physiological aspects that underlie the "Mozart effect" and to the music of Mozart in general—the pleasure, felicity, and depth of emotion of his music can provoke and stimulate a heightened intellectual, even spiritual, awareness and rapture. Perhaps the timeless remark that has been ascribed to the Nobel-prize winning physicist Albert Einstein, himself a genius, resounds most compellingly: "Mozart's music is of such beauty and purity that one feels that he merely found it, that it has always existed as part of the inner beauty of the universe waiting to be revealed."

References

  1. Campbell, D. The Mozart Effect: Tapping the Power of Music, 1997.
  2. Davies, P. Mozart in Person: His Character and Health. New York: Praeger, 1989.
  3. Drake, M. “Mozart’s chronic subdural hematoma.” Neurology 1993; 43: 2400-2403.
  4. Fino, J. and J. Hughes. “The Mozart effect: distinctive aspects of the music–a clue to coding?” Clin Electroenceloph 2000; 2, 94-103.
  5. Jenkins, J. “Mozart–portrait and myth.” J Roy Soc Med2006; 99, 288-291.
  6. Karhausen, Lucas. The Bleeding of Mozart. London: Xlibris Pub, 2011.
  7. Eisen, C. and S. Keefe. The Cambridge Mozart Encyclopedia, Cambridge Univiversity Press, 1997.
  8. Rauscher, F., G. Shaw and K. Key. “Music and spatial task performance.” Nature 1993; 365:611.
  9. Spaethling, R. Mozart’s Letters, Mozart’s Life. New York: W. W. Norton, 2005.
  10. Stafford, W. The Mozart Myths: A Critical Reassessment. Stanford: Stanford University Press, 1993.
  11. Tomatis, A. Pourquois Mozart. Paris: Diffusion, Hatchette, 1991.
  12. Zegers, R. “The death of Wolfgang Amadeus Mozart: an epidemiologic perspective.” Ann Int Med 2009; 151: 274-278.

Vincent P. de Luise MD FACS  is an assistant clinical professor of ophthalmology at Yale University School of Medicine, and adjunct clinical assistant professor of ophthalmology at Weill Cornell Medical College, where he also serves on the Music and Medicine Initiative Advisory Board. A clarinetist, he was the director of the Connecticut Mozart Festival in the bicentenary year of the composer's death, is president of the Connecticut Summer Opera Foundation, and writes frequently about music and the arts

Thursday, October 15, 2015

HIGH TOUCH: THE COURSE IN COMPASSION

Rebuilding a Curriculum of Caring for Healthcare

Vincent P. de Luise,  M.D., F.A.C.S.

Embedding a foundational  "toolkit" of  compassion in present and future physicians  is essential for  improved patient-physician engagement and communication, for physician professional satisfaction, and to prevent physician burn-out. This essay was written as a project paper for the Harvard University Advanced Leadership Initiative in which I was a 2013 Fellow.

 
          "May I see in all who suffer only the fellow human being" 
                                                                           Maimonides                                                 
The Problem

Healthcare is broken and doctors are burning out.

That is the current mantra. Healthcare has gotten too expensive and impersonal, and there is inconsistent access to that care. Doctors are increasingly stressed and do not seem as engaged. Patients complain that their doctors are too busy and no longer listen. They ask, “Who will take care of me as a person and not just as a bunch of x-rays and lab test results?” I trust my doctor, but why does she seem so distracted and disengaged.” With all the technological advances of the last several decades, with genomics and PET scans, MRIs and super-subspecialists for every conceivable body part, what in the world is happening to the very doctors who care for us?  We have all this “High Tech,” but, where is the “High Touch?”  Is being a physician no longer a calling?  Has it become just another job?  Have patients become commodities? Why has doctoring gone astray?   

Gaps

The American system of medicine has become organized largely as a disease-management system, and not as a health-care system, with diagnoses and treatments now reduced to an impersonal set of numerical codes. The concept of “caring” is no longer central to a discussion of “health care.” Patients are being viewed by their health care providers more as the sum of their diagnostic testing, or as the "I-patient," to use the term coined by Abraham Verghese M.D. of Stanford University, which is to say, the "virtual" patient, seen by the physician more through the lens of that physician’s pda, laptop or computer screen, and not as the real, live, hurting individual in front of them.

Of course, this is an oversimplification. There are legions of dedicated doctors who are serving an ever larger and aging population, and who do so with empathy.  But we as a society have indeed reached a watershed moment, a saturation point on many fronts. We now live ever more hectic and hurried lives, with hardly a moment to stop and reflect. With increasing demands on our time and resources, we have become more anxious, are getting less sleep, and are making poorer dietary choices. The cumulative effect of this leads to illness. However, when we get sick, we still want help, and we have come to expect that help to be prompt and caring. Yet, even when we do find that help, it seems to have become curiously robotic and disengaged.

It is crucial for the health care profession – now a health care system, comprised of collaborative teams of physicians, nurses, PAs, social workers, ethicists, and even economists – to remain focused, engaged, vibrant, and committed to caring. We cannot have it any other way. We cannot be a healthy society, with healthy citizens contributing to the success and happiness of that society, without an engaged health care team. We need to (re)-train physicians for a lifetime of caring, so that they continually demonstrate empathy in their work, and so that they themselves remain energized and happy in their careers, as this will improve patient outcomes over time.

Physicians cannot heal without caring, and they cannot care without first being informed by a core set of ideals that will carry through their training and into their professional careers.  Medical schools are set up to train physicians, and at many of them, there is already an awareness of these problems which I have outlined, and some initiatives are in place. But the system, engrained and with its own cultures and rituals and focused on disease management, has lost sight of its ideals, the ideals embodied in the Hippocratic Oath.
 
A Solution: Frameworks in Medical Humanities

We must re-embed a pathway of caring in our health care providers and transfer a lifelong set of skills that will inform them throughout their careers, certainly in the physicians who still lead the health care team. What is needed is an overarching and cohesive rubric, which I have entitled The Course in Compassion: A Curriculum of Caring (The Course). These skills can be identified, quantified and measured, and will populate The Course.  The Course will be divided into modules, and taught using an accepted paradigm in most medical schools, the Problem-Based Learning (PBL) format. Six core modules, which are termed “Frameworks in Medical Humanities,” would be taught over the four years of medical school in weekly two-hour sessions:


                Sensory experience                      Motor task



           Dance and Movement                  Motion Research



           Music Appreciation                      Rhythm/Melody-Making

                                     

           Narrative & Reflective writing       Diary-Keeping



           Mindfulness and Spirituality          Yoga/Meditation 

                                                                          

           Art & Aesthetic Appreciation        Drawing/Sketching



           Empathy Training & Acting          Care-Giving




Stakeholders

Patients, physicians and physicians-in-training (medical students and house officers), medical school administrators, curriculum designers, The Association of American Medical Colleges, state licensing boards, and insurance companies – each of these entities is a stakeholder with a say in physician education. Adopting  The Course will require hours of time to teach its principles, hours that will have to be taken in part from existing core disciplines as anatomy, biochemistry, pathology, physiology and microbiology, as well as from time already assigned to the medical students for hospital wards and outpatient clinics. Conversations will need to occur at many levels to allow stakeholders to “buy-in” to  The Course as a foundational aspect of medical education.

However, The Course does not have to be built “from scratch.”  There exist a number of programs which have pilot projects aligned with my vision and ideas. A number of medical schools (Harvard, Yale, Weill Cornell, Johns Hopkins, Stanford, UCSF, and Columbia, inter alia) offer courses which champion aspects of  The Course. These existing initiatives are already testing the “proof of principle” of The Course. They are virtually all elective (that is, they are not required to graduate), but they exist. Therefore, it is not necessary to “reinvent the wheel” to populate the syllabus of The Course. Rather, The Course would be populated with “best practices” from existing efforts in addition to new initiatives I would add that have not yet been created or tested.

As Harvard Business School Professor Rosabeth Moss Kanter has written, change is often a result of Big Vision and Small Steps.” The Big Vision is creating and curating The Course in Compassion: A Curriculum of Caring (The Course). The small, essential and crucial steps are to pilot a series of medical humanities courses in all six modules, and, utilizing longitudinal data analysis, create metrics to measure patient outcomes and satisfaction over time, and physician satisfaction through their careers.

 Impact
 
“It is far more important to know what person the disease has than what disease the person has.”  
                                                             Hippocrates                                  
 
Medical humanism is a core set of ideals that should be taught from college through medical school, internship and residency, and that should continue to inform a physician through their career. Medical humanism serves as a beacon and lodestone for how physicians listen, respond and care for their patients, as well as providing a road map for the well-being of a physician’s own mind and body over the course of their professional lives. The Course in Compassion will be a foundational paradigm around which physicians can be better engaged, and more motivated and passionate about providing care. Patients will achieve better outcomes, and physicians and their healthcare teams will enjoy longer and more fulfilling careers. This is an initiative which can no longer be fragmented, ad hoc and elective. The Course must become the epicenter of medical education and professional practice.

©   Vincent P. de Luise MD FACS

Friday, September 25, 2015

PLEASURE AND REWARD: WANTING, LIKING AND HEDONIC HOTSPOTS

Vincent P. de Luise MD

What is pleasure?  


Pleasure can mean different things to each of us. For some it might be doing a sport, while for others it could be practicing yoga, eating ice cream, meditating,  sailing  a boat, lovemaking, having a religious experience,  or simply lying on a beach.
The ancient Greeks talked of happiness as being a combination of hedonia (pleasure) and eudaimonia (well-being and human fluorishing by doing "good work" for others).

Certain pleasures have been studied neurologically, using a non-invasive brain scan called functional magnetic resonance imaging, or fMRI. An fMRI scan tracks changes in blood flow (hemoglobin) to various brain regions as a result of a specific stimulus. The more hemoglobin (therefore, the more oxygen) to a specific brain site, the more activity. 


A significant body of scientific research has been published evaluating brain responses to four specific pleasurable stimuli: eating chocolate, listening to music that causes “frissons" (those thrilling “goosebumps” and “chills up or down the spine”  that one gets to particularly pleasurable music), sexual climax,  and,  for those who unfortunately have a need for them, taking addictive drugs, i.e., drugs like cocaine and heroin, which stimulate the brain’s so-called mu-opioid and cannabinoid systems.   

All four of these distinct, pleasure-inducing stimuli (chocolate, music, orgasm, addictive drugs) activate the same brain areas, anatomically adjacent to each other in a region called the medial forebrain (MFB).  These MFB areas are:  1) the ventral tegmental area (VTA) ( specifically a little blob of neurons in the VTA called the nucleus accumbens); 2) the prefrontal cortex; 3) the anterior cingulate cortex (especially its subgenual area, above the nucelus accumbens (not shown));  and 4)  the amygdala.  


Axial transection of human brain       from Harley.com


Pleasure, Reward and the Happiness Trifecta
These four brain areas are part of what cognitive neuroscientists describe as the Reward-Pleasure System. What we feel as desire and pleasure occurs in this system, which is also sometimes referred to as the Wanting/Liking System. This system tells the memory centers in the brain to pay attention to everything associated with that experience, so it can be repeated in the future. The Reward-Pleasure System is activated and controlled by molecular neurochemicals called neurotransmitters, specifically dopamine, serotonin, and oxytocin. Evolutionarily, the Reward System is an ancient pathway: the use of dopamine neurons to interconnect behavioral responses to natural rewards has been observed in various species of worms and flies, whose ancestors were around two billion years ago!

These three neurotransmitters - dopamine, serotonin and oxytocin - mediate every pleasurable moment, including the “giving experience,” so much so that Eva Ritvo M.D., vice-chair of psychiatry at the University of Miami School of Medicine, has termed them the “Happiness Trifecta.” 
 
Dr. Ritvo asserts that "giving is a powerful pathway for creating more personal joy and improving health. Any activity that increased the production of these neurotransmitters will cause a boost in mood and cause happiness." Dopamine is connected to motivation, reward and arousal. Serotonin is connected  to memory, learning, sleep and appetite.  Oxytocin, nicknamed "the cuddle hormone," has a powerful effect on the brain and the body. "When oxytocin begins to flow, blood pressure decreases, bonding increases, social fears are reduced, and trust and empathy are enhanced” Dr. Ritvo explains.
 
Giving to others triggers a release of oxytocin, which boosts mood and counteracts the stress hormone, cortisol. The  higher the level of oxytocin, the more one wants to help others, Interestingly, when oxytocin is boosted, so are dopamine and serotonin. According to Dr. Ritvo, "even small repeated boosts of the Happiness Trifecta will produce a benefit. Donating money or time... are wonderful ways to give. When we step outside of ourselves long enough to help someone else, something wonderful is waiting for us when we return: the Happiness Trifecta neurochemicals are all boosted ! "


Nerve-nerve cables, called neural networks, interconnect the pleasure centers. These neural networks work electrically, as well as chemically through the neurotransmitters.  When we experience pleasure, we are, in essence, getting a reward.  

Much of pleasure has to do with what cognitive neuroscientists call the "Wanting/Liking" system in the brain, which is part of the "Reward-Pleasure" circuit.


Hedonic Hotspots, Enkephalins and Anandamides


Things are actually a little more complicated than the Happiness Trifecta of dopmaine, serotonin and oxytocin. University of Michigan researchers Morton Kringelbach, Terry Robinson and Kent Berridge have discovered that there are neurochemical differences in our brains between “wanting” something and “liking” it.

The “Wanting”  or "Desire" part of the system is largely mediated by dopamine, the same neurotransmitter that is involved in drug addiction with cocaine and heroin. Dopamine, according to Berridge, contributes more to motivation ("Wanting") than to the actual sensation of pleasure ("Liking") itself.


The “Liking" (or "Pleasure") system” in the brain is mediated by  neurotransmitters called enkephalins and anandamides. There specific areas in the brain which have dense populations of these neurotransmitters. These areas serve as waystations for "Liking."  Berridge calls these “Liking" system brain areas “hedonic hotspots.”   ("hedonic” means "pleasant" (recall the ancient Greeks, hedonia, and our modern-day notions of  hedonism).

The enkephalins bind mostly to what are known as opioid (mu-opioid) receptors in the brain. The anandamides, in contrast, bind to cannabinoid receptors. They are termed cannabinoid because they are similar to receptors which bind the cannabinoids  (molecules which are also contained in marijuana). Yes, we humans make our own opioids and cannabinoids in our brains, in much smaller concentrations than if they are taken externally. Nonetheless, isn't it fascinating that opioids and cannabinoids are endogenously manufactured in our brains !?


Two key hedonic hotspots in the brain are a specific region in the nucleus accumbens called its medial shell, and another area, the ventral pallidum, which is right below the nucleus accumbens (and different from the ventral tegmental area discussed earlier).

A bite of chocolate, for example, prompts neurons in these hedonic hotspot areas to release neurotransmitters in the encephalin family,  which are endogenous opioids that are made in our brains. According to Berridge, these enkephalins then interact with receptor proteins that cause the release of anandamide, our brain’s own home-made version of a marijuana cannabinoid. The anandamide, in turn, can interact with other neuronal receptors, producing more enkephalin and intensifying the pleasurable experience.

Interestingly, these anandamide (cannabinoid) receptors are located much more densely in the cerebral cortex ("the "thinking brain") than in the limbic system of the mid-brain (the "subconscious brain"). 

What does this mean? It means that when we desire, seek, or are motivated for pleasure, we release lots of dopamine to get what we want. When we get what we want ("sex, drugs, rock and roll," and chocolate), we really like it, through the release of enkephalins and anandamides. 


It turns out that, among these stimuli, it is music that is particularly exciting to an individual, especially music that causes those "chills" down the spine. Music is a powerful stimulus of the pleasure center in the brain, engaging the same receptors in the same brain loci as drugs, sexual climax and chocolate. 

Why would that be?  

What is the role of music in our evolution? Are humans hard-wired for music? Music may have a foundational and evolutionarily adaptive role in our brains. 

That is the topic for the next A Musical Vision essay.
@ Vincent P. de Luise MD 2015

Kringelbach, M. and Berridge, K., The Joyful Mind, Scientific American, August 2012.