About neuroscience and music (mainly classical). Exploring the relationship of music and the brain based on experience of two careers.

October 11, 2017

Have you Lost Your Sense of Smell?

I still can’t get my mind around the fact that a mysterious agent, whatever it is (or they are), that can cause Parkinson’s Disease (PD) probably enters the body through the nose or the mouth. It, or its evil effect, travel to the brain through the olfactory or the vagus nerves, the former from the nose, the latter from the gut! 

That initially outrageous idea reminds me of a similar drama decades ago when we all knew for sure that stomach ulcers were caused by stress and too much acid. We were shocked when courageous researchers steadfastly asserted that helicobacter pylori, a typical bacterial resident in the stomach usually minding its own business, could occasionally go berserk and dig a hole. Now we add antibiotics to our treatment regimen for ulcers!

A PD agent is probably not a bacterium, virus, or even a tiny newly-discovered prion, but it could behave like H pylori. Or like a zebra mussel, living a quiet peaceful life in lakes in another continent only to become aggressive and devour all its neighbors when introduced into the apparently nurturing environment of the American Great Lakes. (Dr. Siddhartha Mukherjee just used that analogy to try to understand the behavior of some metastatic cancers in last week's New Yorker.) Perhaps certain people are destined for Parkinson's because they unknowingly provide a similar favorable environment for mysterious agents that may be ubiquitous and harmless for most other people.

A recent editorial in NEUROLOGY reminded me that although loss of the sense of smell becomes increasingly likely as we age (isn't aging a relentless wearing-out process?) a substantial (but yet unspecified) proportion of people with hyposmia (reduced) or anosmia (absent) develop Parkinson's, or some form of dementia, possibly including Alzheimer's. My father lost his smell years before symptoms of his dementia appeared in his late '80's. As I pointed out in a previous post, loss of hearing too is not necessarily a 'normal' or inevitable part of aging.

Detecting the earliest evidence of Parkinson's disease among healthy patients could help us test and develop methods to prevent or slow future progression to the typical disabling features of the condition, such as impairment of walking, moving, thinking, and speaking, and tremor, before those symptoms appear when the loss of the critical dopaminergic neurons in the midbrain is complete. According to one hypothesis (Braak), the process usually starts low in the brainstem and very slowly marches upward over years. When it reaches the cerebrum, if you are still alive, the 'late' complication of dementia may ensue 

Degeneration of the olfactory bulb (a tassel-like structure attached to the bottom of the brain just above the nasal cavity) is a common cause of impaired sense of smell and may provide the earliest clue to future PD. The bulb rests upon a thin fragile plate of bone punctured by tiny holes, the lamina cribrosa, through which wire-like nerve fibers (axons) transmit olfactory signals from 6–10 million smell receptors in the nose. 

The olfactory nerves are also called the first cranial nerve (the second transmit vision and the eighth bring sound into the brain); transmit signals gathered by the receptors from the bulb to the brain. (All cranial nerves are paired, one on each side.)

Once an odorant enters the nose, it interacts with the receptors located on the surface of the olfactory cilia and a chemical reaction generates a crescendo of action potentials (signals) in the olfactory nerve. These signals project to higher brain regions involved in conscious thought processes and the limbic system, generating the emotional, motivational, and memory context. 

Approximately 1,000 of human genes participate in recognizing odors. Thus, we can distinguish 4,000–10,000 distinct odor molecules, a scientific discovery that earned a Nobel Prize in 2004. 

Olfactory dysfunction impairs the satisfaction gained from foods and inhibits the detection of environmental hazards (e.g., toxins, fire, spoiled foods, and natural gas leaks). Diminished olfactory inputs also dampen the initial phase of digestion responsible for stimulating exocrine secretions in the mouth, stomach, the secretions that facilitate the absorption and assimilation of micronutrients and fatty acids and contribute to the nature of the microbiome in the host by governing the gut pH.

The prevalence of all-cause hyposmia in the US adult population is discouragingly high: between 13.5% and 24.5%, and increases incrementally with age (17.3% of 60- to 69-year-olds, 29.2% of 70- to 79-year-olds, and 62.5% of 80- to 97-year-olds). Men and African Americans have the highest prevalence of hyposmia. Only 9% of adults actually report a loss in their sense of smell, an observation that suggests a substantial number of cases go undetected (and that a substantial number of people old enough to afford wine judge its quality only by the price of the bottle).

Ninety percent of people with sporadic (not familial) PD, have olfactory dysfunction. In addition, 4 prospective studies have shown that olfactory dysfunction is a risk factor for PD, but the conclusions drawn are almost exclusively from white and Asian populations with less than 5 years of follow-up. It turns out that African Americans have a higher rate of olfactory dysfunction but a lower risk that it will cause PD.

One underlying mechanism behind olfactory dysfunction in PD is the spreading and accumulation of Lewy bodies, enriched with intracytoplasmic inclusions of α-synuclein that arise from peripheral inputs at the olfactory epithelium or the dorsal motor nucleus of the vagus nerve emerging from the stomach.

If you read this and know, or discover, or suspect, that you have impaired sense of smell, don't panic. Among those percentage ranges above, the data does not allow us to separate those with a risk of any neurologic disease, though one can suspect that  the risk is greater if you fall into one of the younger age groups. It is important to be aware of the problem, in case preventive therapy emerges, and to rule out common non-neurologic causes, such as a lifetime of repeated or chronic upper respiratory infections. 

Most doctors, even neurologists, don't test for hyp- or anosmia and that's a shame. The first step in a test would be to ask a simple question: "How is your sense of smell?" If the answer is not "great," then simple office tests, like The Brief Smell Identification Test (BSIT), can quickly and accurately detect and roughly quantitate the degree, just as an audiogram or vision test does.

As of today, we don't have any treatment that will prevent Parkinson's but it is only a matter of time until we do. That might prove to be an active therapy or strict avoidance of a possible multitude of agents -- in the air or food -- that may be a cause. Scott Pruitt and his EPA are now probably going to provide us with more cases for study.

April 20, 2017

"Coachella is Certainly a Place to See Live Music...."

I try to hard understand the enormous changes in music taking place during my lifetime. As an child, I loved hearing the Cleveland Orchestra in my hometown, but the music that orchestra makes today, though by some measures at an even higher level, is no longer what most people mean when they play or speak of “music.” 

Performing arts organizations of all sizes, from small Music at Gretna to the massive Metropolitan Opera are scrambling to retain audiences to support their missions without having to drain dry the wells of patronage. For too many people our music tends to be “classical” in the worst sense of that term: old music outmoded and forgotten. I find myself a little sheepish when I respond to the question: ”What kind of music do you play?” The response is usually a conversation-stopping, “Oh.”

That all came up again this week in my winter hometown, Palm Springs California. The Coachella Valley Music and Arts Festival ("Coachella") came to Indio. Though that is 22 miles away, many of the expected 200,000 "fans" paying at least $400 for general admission, some arriving in VW vans, some on commercial flights, some in private planes from LA or Bermuda, spilled out into the restaurants and hundreds of hotels in Palm Springs. The promoters expect to "gross" way over $100 million and pay headliners each $3-4 mil to perform. The 345 restrooms and 6 stages inside huge tents on 700 acres of desert are astounding. The event presents "a whirlpool of commercial potential" according to The New Yorker.

Read more by John Seabrook and Carrie Battan

January 26, 2017

Abbado, Lucerne, Mahler

Just before the New Year I purchased a DVD of Claudio Abbado conducting the Lucerne Festival Orchestra in Mahler's Ninth Symphony. The Ninth was Mahler's farewell to the world: "Each passing minute takes us closer to the grave. Death is awful in its inevitability. We will rage and fight against it, but in the end, something bigger than we can imagine will force us into acquiescence." (Shirley Apthorp in the liner notes) 

The 'Ninth,' probably in the Bernstein recording, gave rise to the despondent "Late Night Thoughts While Listening to Mahler's Ninth Symphony" by Lewis Thomas, contemplating late in his life the possibility of nuclear armageddon that seems to have crept back into my consciousness since November 4. 

Mahler's end was premature in 1911 at age 51, caused by subacute bacterial endocarditis, a condition from which he could have been saved 50 years later by antibiotics and, if also needed, cardiac surgery. Abbado was about 76 years old when he conducted this recording, five years before his more timely, but no less regrettable, end.

The performance, in contrast to the Bernstein recording, is, according to Apthorp, "fluid" rather than "angular," "driven" rather than "accepting," and "talkative" where Bernstein was "silent." However you try to describe it in mere words, the amazing performance kept our entire party on New Years Day totally rapt after dinner. No one asked to me to check football scores! We all respected the "Abbado Pause" -- after the last quiet note died away. Speechless, we wiped away tears.

Everything about the DVD is exquisite: the musicians, hand-picked from the best orchestras in Europe; the filming that, I hesitate to say with Lucerne on my bucket list, offers many advantages over what any member of the large audience in the hall, Kofi Annan and Simon Rattle included, was able to experience; the sound, better of course on a good system but lush and full with earbuds; and especially the view from all angles of Abbado conducting without a score a work he has known all his life. Orchestra members, entirely immersed in the music, effortlessly moved and swayed with him.

Armageddon is not part of the business model of Amazon. Within days my inbox delivered an offer: Mahler Symphonies 1-7 recorded at the Lucerne Festival by Abbado and his orchestra. I snapped up a "like-new" package of 4 DVD's from one of the "other vendors" for $43 plus shipping! I only discovered several weeks after it arrived that the producers had slipped in a bonus Prokofiev Third Piano Concerto by Yuja Wang and Five Rückert Songs by the sublime Magdalena Kožená, mentioned only in small print on the album cover. 

More art has probably been inspired by the Resurrection than by any other 'event' in human history. None comes closer, in my view, to matching the profundity of that idea than the recording in this set of Mahler's Resurrection Symphony, No 2. Mahler was, of course, born into a Jewish family. Why can I not understand why anyone experiencing these performances might not be overwhelmed by humility? 

I will not "rage and fight" against death when that time comes. But I will include these amazing recordings on my final "playlist."