AMERICAN SCIENTIST: MACROSCOPE
The Widening Gyrus
Concert pianists could be model organisms for studying the physiological basis of intellectual greatness
An old question: What accounts for highly intelligent and greatly gifted individuals? Three centuries ago, phrenologists thought that geniuses could be distinguished from criminals by the shapeliness and bumpiness of their skulls. When Charles Darwin’s head was considered by a German psychological society, one member declared that Darwin “had the bump of reverence developed enough for ten priests.” In 19th-century Europe and America, a number of distinguished academics bequeathed their brains for anatomical study—Gauss, Broca, Gall, Pavlov, Osler and others. Some probably sought to leave behind posthumous confirmation of their own genius. Originally, the anatomists compared gross weight and volume of brains and made what they could of the various lobes and surface convolutions. With the advent of microscopic anatomy, they were able to look for histological differences, yet by 1928 researchers were concluding that nothing in these early studies provided “a basis from which mental abilities [might] be inferred.” However, neurophysiologists of that era were beginning to identify specific areas of the brain responsible for general motor function and sensory activity. In recent decades, neurohistologists have developed cytoarchitectonics, enabling them to count neurons and support cells—oligodendrocytes, astrocytes and glial cells—in different areas of the brain. And during the past decade, brain imaging with positron emission tomography and functional magnetic resonance imaging (fMRI) has allowed noninvasive localization of various functions and responses. Even with these new tools the essential question—whence talent?—remains an enigma.
The most revered modern genius was Albert Einstein, who died at age 76 in 1955 at Princeton. His brain had a circuitous fate; for several years it rested in a jar of formaldehyde in a Kansas closet, was later carried to Berkeley and is now preserved in Hamilton, Ontario. At McMaster University, Einstein’s brain was compared with brains of an age-matched male group. It was within normal limits except for the parietal lobes, which were 1 centimeter (15 percent) wider than that of the control group. This region of the brain is responsible for visual-spatial cognition and mathematical thinking, and according to Sandra F. Witelson, presumably achieved its distinctive form early in Einstein’s life, based on the understanding at that time of cerebral development. Each of Einstein’s posterior parietal lobes consisted of one distinct compartment instead of the usual two separated by the Sylvian fissure. Earlier, at the University of California, Berkeley, Marian Diamond and coworkers had reported that the isocortex (the outer six layers of gray matter) of Einstein’s left parietal lobe (Brodmann area 9) contained 77 percent more glial cells per neuron than brains of 11 normal males aged 47 to 80. This ratio “suggests a response by glial cells to greater neuronal metabolic need … [and] might reflect the enhanced use of this tissue in the expression of his unusual conceptual powers.”
Ranking surely with mathematical geniuses in intellectual stature are people with acute musical ability, such as eminent composers, conductors and concert performers. For great pianists, several functions are involved: hearing/perception/appreciation, memory and performance. Hearing involves the primary auditory cortex, which is confined largely to the anteriomedial region of Heschl’s gyrus (anterior transverse gyrus of the temporal lobe). A study published in Nature Neuroscience in 2002 reported that this gyrus is 2.3 times as large and twice as active in the brains of professional musicians as in nonmusicians, suggesting plasticity in human brains expressed under conditions of intense musical training. The histologic nature of that increase has not yet been studied.
In the mid-19th century, Jean Pierre Flourens (1794–1867) maintained that cognitive functions are the integrated activity of the entire brain. And recently, Nobel laureate Eric Kandel and psychiatrist Larry Squire reiterated the point that “Memory is not a unitary faculty of the mind but is composed of multiple systems that have different logic and neuroanatomy.” For example, memory involves two systems: short- and long-term memory, which are located in different regions of the brain. Long-term memory consists of two types: explicit/declarative/conscious recall of facts and events, and implicit/nondeclarative/unconscious recall of motor skills, habits and so on. Both types have been localized by various authors in the isocortex of the “upstream” brain regions—specifically, in the frontal and parietal cortices and medial temporal lobes. Complicating the study of memory storage is the assumption that remembering “what” and “how to” are different matters that may be centered in different regions of the neocortex. At present it is unknown to what degree the association areas for specific memories are circumscribed. For example, we don’t know whether the remembered experience and knowledge of a Chopin étude resides in the same region of the cortex as a Bach prelude.
Concert pianists not only memorize massive amounts of music, they also engage complex motor skills, as both hands play different notes and chords, often at high speed and with different tempos and rhythms, while their feet work the piano’s pedals. It is reasonable to suppose that certain areas of the motor cortex of concert pianists are very highly developed.
The localization of motor function began when Flourens’s French countryman, Marc Dax (1771–1837), reported aphasia in right-handed patients suffering a stroke with right hemiplegia—that is, disability due to some left hemisphere injury. Several decades later this observation was corroborated by Paul Broca (1824–1880), and the motor speech area in the left cerebral hemisphere was eponymized as Broca’s area (left inferior frontal gyrus). The localization in the brain of sensory and motor functions engaged early neurophysiologists, but of late they have focused more on localization of memory. Compared with memory and hearing (meaning the entire complex response to auditory stimulation), motor functions may be more localized and possibly easier to investigate. They have been mapped out in discrete projection areas on the cerebral hemisphere’s surface, as depicted by the famous motor homunculus devised by the neurosurgeon Wilder Penfield(see figure at right).
The process by which fine motor skills are honed may have parallels with how memory storage is increased, hence the preceding digression. The mechanisms proposed for enhanced memory have centered on one of two alternative explanations: existing synapses may change as a result of changes in local gene expression, yielding new proteins and possibly increasing the number of vesicles near the presynaptic membrane, and/or new synapses may be generated (synaptogenesis). In memory studies little attention has thus far been given to a third possibility: neurogenesis. In key motor areas, increased synapses and increased synaptic efficiency may account in part for piano virtuosity, but I suggest that neurogenesis should also be considered.
Plasticity in the Adult Brain
The dogma of neurophysiology up until the 1970s was that generation of new neurons was limited to the period of embryogenesis for most of the brain, with a few exceptions, including the granule cells of the olfactory bulb and hippocampus. After birth, regeneration of neurons was believed to be limited to the peripheral nerves. As it became clear that all cortical areas of the brain exhibit plasticity (changes over time), modulations in function and activity were ascribed to synaptic changes. However, recent studies have suggested that neurogenesis may also be in play. Following are nine reports that describe simple enlargement of the brain or an increase in the volume of specific cortical areas after various stimuli. In the first four reports neurogenesis was not considered by the researchers; in the latter five reports, it plainly occurred.
In the early 1980s, William Greenough and colleagues trained adult rats on multiple maze patterns and found that afterward, “visual cortex pyramidal neuron dendritic fields were larger” than in controls. Rats trained on complex motor tasks also showed greater “cerebellar cortex thickness” than control rats given “far more physical activity” using devices such as treadmills. According to the authors, the results “strongly implicate changes in the number of synapses in the memory process.” They did not pursue a conclusive histological investigation.
In the 1990s, Gregg Recanzone and coworkers trained monkeys “to discriminate between two vibrating stimuli applied to one finger” and after several thousand trials found that “the cortical representation of the trained finger became more than twice as large as the corresponding areas for other fingers.”
In 1995, Thomas Elbert used neuroimaging to study right-handed string musicians and found that “the cortical representation of the fingers of the left hand … was larger than that in controls.”
In 2004, Bogdon Draganski and colleagues employed fMRI scans of young volunteers who had mastered over a three-month period “a classic three-ball cascade juggling routine” and found expansion in gray matter in the mid temporal area and left posterior intraparietal sulcus. Notably, the expansion decreased three months later.
In the following five reports, postnatal neurogenesis was explicitly addressed.
Studies by Fernando Nottebohn in birds may have relevance to neurogenesis in the human brain. In the early 1980s, Nottebohn’s lab reported in several papers that in the female canary forebrain (hyperstriatum), the volume of two vocal control nuclei (functional collections of neurons and associated cells) increased markedly during the peak of the singing season, then declined, then increased again during the successive singing season. The song repertoire of the canaries changes each year. The birds were injected with 3H-thymidine, which becomes incorporated in the DNA of replicating cells. In birds that received the label, it was shown that the volume increase in one particular area was accompanied by labeled glial, endothelial and migrating neuronal precursor cells—all of which were interpreted as signs of neurogenesis.
The earliest neurological studies using radioactive labeling were done in 1962 by Joseph Altman, who injected 3H-thymidine into lesions created in the lateral geniculate body of adult rats. He found labeled glial cells, neuroblasts, and a few neurons in or near the lesion area. The presence of labeled neuroblasts was judged to support “a process of neurogenesis” in the area of repair.
In 1999, Elizabeth Gould and coworkers injected bromodeoxyuridine (BrdU, a synthetic nucleotide analog that, like 3H-thymidine, gets incorporated into DNA in replicating cells) into adult macaques and after one week found labeled mature neurons in the prefrontal, inferior temporal and parietal cortices, indicating that neurons “are added to primate neocortex in adulthood.” The authors did not regard the prior studies by Altman and Nottebohn as definitive or as establishing neurogenesis.
Peter Ericksson and colleagues reported in 1998 on the injection of five terminally ill patients with BrdU. They found that after their deaths (from several weeks to two years later), cells in the hippocampal dentate gyrus were labeled with both BrdU and a neuron-specific marker. They interpreted their findings to indicate the “genesis” of new neurons from “dividing progenitor cells” in the gyrus.
Finally, work by Marian Diamond and colleagues indicated that the continued growth of human brain after birth is influenced by nutritional factors and environmental influences. They found that rats given playthings and treadmills (“an enriched environment”) develop more glial cells per neuron in the occipital cortex. Other changes noted were “neuronal stroma size, neuronal density, length of dendritic branches, dendritic spine density, length of synapses and glial cell counts.”
The Brains of Concert Pianists
It is now recognized clinically that the human brain has remarkable plasticity and potential for restoring lost function. Following localized injuries to the brain, neurological deficits can often be ameliorated by special training. In other words, changes in the brain can be electively produced. Compensating for lost function is one thing, but what would we expect to find in healthy people who perform mentally demanding, fine movements (for example, typists and musicians)? Do they develop discernable and consistent morphological changes in certain motor areas of their brains?
Pianists were considered good candidates for studies of this sort early on. In the 1920s, Rudolf Klose examined the brain of a young piano prodigy, Goswin Sökeland (1872–1900), but reported (in five densely packed German pages) only the gross morphology—“der Gyrus supramarginalis ist ganz enorm entwickelt,” and so on. Today a detailed brain study of highly proficient pianists would examine neuronal topography and other details of fine structure and might disclose additional distinctive features in that ganz enorm gyrus.
One current consensus of neurogenesis is that new neurons may result from the transformation of stem cells and their migration into relevant sites. The physiological basis for these changes has yet to be defined but may involve adjacent accessory cells releasing chemical factors and/or endothelial cells stimulating the growth of new circulatory vessels (angiogenesis).
Circulation in the Brain
The neuropathologist Alfred Meyer referred in a footnote to a work from 50 years before by B. K. Hindze of Moscow, “who had shown that in brains of persons of outstanding ability the arterial supply is more elaborate than in brains from persons of mediocre ability.” But this study was “too small to permit definitive conclusions.” In 1974 a report described blood flow in the brains of patients with chronic schizophrenia, and another report examined blood flow in normal persons in the hemisphere associated with speech and reading. Both studies used the Xenon-133 method with 32 detectors placed alongside the patient’s head. In the latter report the authors stated, “The blood flow of the brain is ultimately regulated by the metabolic activity of the neuronal tissue.” A 2008 paper by Fred Wolf and Frank Kirchhoff measured blood flow by fMRI and asserted that “astrocyte activity affects local blood flow.” Not reported in these studies is whether increased blood flow occurred via existing capillaries or newly formed ones—the latter arising perhaps in a process analogous to tumor angiogenesis. A reciprocal consideration is whether increased blood flow in an area might stimulate further neuronal or astrocyte development there, just as, in certain solid tumors, increased blood flow allows proliferation of malignant cells.
Michael Chopp and colleagues have recently examined agents that promote neurogenesis and angiogenesis during recovery from strokes induced in animals: “Matrix metalloproteinases expressed in the periinfarct vasculature are chemotactic for neuroblasts migrating from the subventricular zone.” Here angiogenesis was monitored by MRI.
Concert pianists represent a human model of highly integrated motor activity. The primary motor area for the hands and arms is in the precentral gyrus of the frontal lobe. If an fMRI of this area in trained pianists reveals increased blood flow, we may question whether it is due to neocapillaries induced earlier by an angiogenic peptide—similar to the macrophage-derived angiogenesis factor or tumor necrosis factor alpha. Angiogenesis has been studied extensively in certain brain tumors (glioblastomas) and recently in cases of stroke—both pathological conditions. This essay suggests a nonpathological function for angiogenesis in the healthy, stimulated brain.
Searching for a talent-linked angiogenic peptide (or peptides) in neurogenesis would be difficult using master pianists as the model. Concert performers are rare and revered and might resent neurochemical probing of their brains. Furthermore, the development of their enhanced motor skills takes place over many years of practice. This long interval might make identifying a putative angiogenic peptide difficult if it were present and active only with the inception of the new capillaries. On the other hand, it seems plausible, based on work such as Nottebohn’s birdsong studies mentioned above, that maintaining a high level of pianistic skill requires continuous stimulation by an angiogenic factor for preservation of an enhanced local capillary bed.
My fascination with this subject developed after attending a private performance by Dr. Paul Bachner, chair of pathology at the University of Kentucky and a gifted concert pianist. It would be interesting, if intrusive and perhaps unwelcomed, to determine if his pianistic skill is linked to high levels of a cerebral angiogenic peptide.
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