CROTCHETS & QUIDDITIES

What Stamps the Wrinkle Deeper on the Brow?KENNETH WEISS AND KRISTINA ALDRIDGE

In a noteworthy 1935 book, LudwikFleck wrote that what science acceptsand interprets as “fact” is not purelyobjective, but is a product of the his-tory and underlying theory of the sci-ence at the time.1,2 Contextual andeven subjective factors drive, mold,and constrain scientific inferencemore than we may realize. Fleckshowed how scientific illustrationsserve as ideograms that reflect but alsosubtly promote the prevailing world-view. This conveys information butalso channels thought, because in de-ciding how to represent a phenome-non some features are made more ob-vious while others disappear. Theresulting presentation can have se-ductively proliferating effects. Whatwe see in graduate school can staywith us a long time!

Fleck was not an evolutionary biol-ogist but historical sciences may bemore vulnerable to being prisoners oftheir theory—interpretive preferenc-es—than experimental sciences likechemistry or physics. This certainlypertains to evolutionary anthropol-ogy, where our endless argumentsabout what is or isn’t visible in a fossil

specimen generally depend on visualpresentation and assessment. Multire-gional continuity, or replacement?Human ancestor or side branch? Ro-bust or gracile? Bipedal?

Fleck singled out anatomic illustra-tion to make his points. One examplewas the depiction of the surface anat-omy of the cerebral cortex. Evensomething so seemingly straightfor-ward shows how ambiguous or theo-ry-dependent a simple illustration canbe, in regard both to function and evo-lution. Interpreting past representa-tions is problematic because we can’treally know what preconceptions theauthors might have built into them(intentionally or otherwise). But thesame is true today. What evidentiarycriteria might we apply to determinewhat can, or should, be included in amodern representation?

FROM VESALIUS TO NOW

In his gloriously illustrated 1543anatomy text, Vesalius3,4 drew thesurface patterns of the brain to show“the appearance of coils of intestine oreven more to clouds outlined byschoolboys or unskilled art-students,”giving little importance to specific fea-tures (Figure 1). Fleck notes that Ve-salius and even ancient classical au-thors had portrayed schematic, ratherthan literal, details of the cerebral sur-face. Today, we dismiss a disregardfor detail as art rather than science,less “real” than modern illustrations(http://www.nlm.nih.gov/exhibition/dreamanatomy/index.html). But are

more literal representations more cor-rect than Vesalius was?

One need look at no more than twobrains—even if they are identicaltwins—or even just left and right sidesof the same brain to see that the sur-face features vary considerably fromperson to person (Figure 2).5 Both theoverall convolutional complexity andthe details vary. Not surprisingly, vari-ation among species is even greater(Figure 4). But it is not clear whataspects of this variation are importantto include, and how less importantfeatures should be presented so as notto misrepresent the brain. Perhaps weshould turn to evolution, because iffunctionally relevant traits have beenmolded by natural selection theyshould have a genetic and specific de-velopmental basis today.

We can frame such a search aroundsome rather general aspects of thebrain about which there is at leastwidespread implicit agreement: 1)The brain has multiple distinct func-tional capabilities; 2) being distinct,these could be expected to “map” (belocalized) in the brain; 3) broadlyspeaking, the size of the relevant areawill reflect aspects of function; 4) localsize variation should affect the overallshape of the brain; and 5) because theskull and brain develop together, theymay influence their respective shapes.

DEVELOPMENT: SULCIAND GYRI

Developmental studies have shownthat the surface of the cerebrum issmooth until the appearance of thelateral sulcus (Sylvian fissure) in the4th gestational month, followed rap-idly by the other primary sulci (e.g.,central pre- and post-central sulci, in-traparietal, frontal). Secondary andtertiary convolutions continue to ap-

Ken Weiss is a biological anthropologistat Penn State.Kristina Aldridge is a graduate student inthe Center for Functional Anatomy andEvolution at Johns Hopkins University.

Evolutionary Anthropology 12:205–210 (2003)DOI 10.1002/evan.10122Published online in Wiley InterScience(www.interscience.wiley.com).

Science often relies on simplified diagrams to convey information, but these canembed tacit assumptions. A good example is provided by the surface convolutionsof the cerebral cortex. It is surprisingly difficult to know what these features mean,and which deserve evolutionary explanation.

Evolutionary Anthropology 205

pear long into the postnatal period.The primary sulci tend to be deeperand are generally the most stablewithin and among species, and de-velop earliest ontogenetically (Figure3). Compared to these, the other fea-tures are the dirt roads of the brainatlas, some being too variable to bedepicted accurately in a single illus-tration, while others are deemed—rightly or wrongly—too unimportantto be specifically named.

Despite some conserved features,there is still a remarkable degree ofvariability among primate brains, assuggested by Figure 4, picturing MRIs(magnetic resonance images) of 10anthropoid species. There are differ-ences in size, the degree of convolu-tion, presence of specific sulci, anddepth of sulci present. However, thesevariables do not show entirely clear orconsistent relationships with eachother, or with phylogenetic distance,so their adaptive interpretation or im-

portance are unclear. Some authorshave suggested that convolutions ap-pear to be located in different placesin humans than other species, or thata given sulcus is longer or deeper. Thehuman brain is somewhat more con-voluted, which under the assumptionthat increased convolution leads to in-creased cortical surface area, has beeninferred as implying greater intellect.This is an understandable inferencegiven our anthropocentric obsessionwith the brain as our evolutionary rai-son d’etre (whatever happened to thethumb?).

However, it is not obvious whatthese observations mean because, be-yond the primary features, theamount of variability makes it unclearhow many sulci are homologousacross species, as opposed to just be-ing in roughly the same location, andbigger brains are not inevitably moreconvoluted within a given taxon orgroup. Depending on what biologicalprocess causes the sulcus, location perse may not even be a good criterion forassigning homology; for example, ho-mology might more properly be asso-ciated with the underlying function,cytological cortical structure, or de-velopmental processes that resulted ina given fold. These questions have notyet been answered, but every line in

Figure 1. Ideograms or truth? Vesalius captured impressions. Was he wrong? (Source:Vesalius, 1543)

Figure 2. Variation in brain surface anatomy. (A) Left-right variation; (B) Identical twins; (C)Unrelated individuals. (Credits: B, C.5)

206 Evolutionary Anthropology CROTCHETS & QUIDDITIES

an illustration is a statement aboutthem.

Stuff and Nonsense?

The major lobes of the telencepha-lon (forebrain) are produced by anearly developmental patterning mech-anism involving the expression andquantitative interactions among sig-naling and gene-expression factors.6

But is the developmentally later for-mation of the sulcal/gyral pattern anelaboration of that same process? It isgenerally thought that sulci are pro-duced by differential growth of thecortex, with some areas expandingfaster than others. The reason is amatter of debate, and several plausi-ble alternatives have been suggested.

One hypothesis is that gyri areformed through localized growthspurts of cortex, leaving valleys ofslower growing cortex between them.In this view, the convolutions are sim-ply a random “stuffing” phenomenon:as the brain grows inside the con-straining braincase, it folds much aswould occur when cramming moreand more clothing into a laundry bag(this may also change the shape of thebag itself). The random-like appear-ance of tertiary convolution had beennoted by the early 1900s. Tertiarysulci develop during the early postna-tal period when the braincase has es-sentially closed; however it is notcompletely clear that the braincase is

a constraint, because both it and thebrain grow during this period. Alter-natively, the locations of sulci may bedetermined by growth of the subcor-tical structures. This idea is that thecortex is “anchored” by adjacent sub-cortical structures (creating a depres-sion—sulcus), with surrounding areasallowed to experience growth (creat-

ing a bulge—gyrus). One might thinkof this as cords constraining the bil-lowing brain growth, much as cordsrestrain the shape of a billowing para-chute, or as the frontalis muscle (lit-erally) furrows the brow. A third pos-sibility is that the cortex “buckles” invarious places, based upon differen-tial growth of the internal versus ex-ternal layers of the cortex itself.

These three views are not mutuallyexclusive; different convolutionsmight be produced by different pro-cesses. Demonstrating a random com-ponent, if it exists, may not be easybecause it would require specificationof reliable landmarks, and hence ho-mology, about which there is not uni-versal agreement.

GENETICS: VAGUE BUTSIGNIFICANT EFFECTS

Whatever their developmentalcause, if the pattern is of evolutionaryimportance, its basis should be genet-ic—transmitted from parent to off-spring, rather than just being theephemeral products of chance duringan individual’s lifetime. If the tertiaryor even the secondary convolutionpattern is just a random stuffing phe-

Figure 3. Some primary sulci of the human brain.

Figure 4. Variation among primates. Not to scale. (Credits listed in the acknowledgments.)

CROTCHETS & QUIDDITIES Evolutionary Anthropology 207

nomenon, it may have no functionalconsequences and have been of noconcern to selection. If so, then mostbiologists would consider it not to bean evolutionary trait. But this wouldnot be the usual assessment, becausecortical convolution is so pronounced,and it is generally agreed that bothlocalized function and its variationare evolutionarily important. A num-ber of studies have sought to find ge-netic effects by comparing related andunrelated individuals (typically identi-cal twins to unrelated people or pairsof dizygous siblings). The tested traitshave included multivariate metricscoring of cortical thickness, volume,or overall shape, sulcal mark-points,sulcal depth, or underlying MRI-scored brain shape.

Sample sizes have been small butresults are broadly consistent.5,7,8

Brain size, volume, and overallshape seem to be under strong ge-netic control. The most heritableconvolution structures are those thatdevelop earliest, formed by the ma-jor lobal divisions. These deeper,longer, traditionally named sulciseem highly genetic (although in onestudy of macaques sulcal length didnot seem heritable.9) This is satisfy-ing because it is consistent withtheir shared presence within hu-mans and among primates.

The story is less clear for the subtlerfeatures. Heritability estimates for ter-tiary gyri and sulci are lower, thoughthey can be statistically significant.Convolutional complexity is roughlycorrelated with overall shape, which isstatistically heritable. Tertiary featuresvary more than other features betweenleft and right sides in the same personand between identical twins (Figure 2),but contralateral features are correlatedwhen comparing MZ twin sets,5 sug-gesting genetic effects. Numerous local-ized areas of the cortex have beenshown to have detectable heritabil-ity.10,11 However, their relationship tospecific structure of the overlying gyri isdifficult to evaluate, in part becauseheritability is an overall statistical mea-sure: individual gyri occur in variablelocations among individuals, makingcomparison difficult. Nonetheless, mea-sures of overall sulcal similarity haveshown statistically significant heritabil-ity.7

So much for location. Do these ge-netic effects on shape have anythingto do with brain function? MZ twinsvary in the left-right asymmetry asso-ciated with handedness.12 Variationbetween MZ twins isn’t genetic, butsome brain asymmetry does appear tobe affected by genes.11 Genetic influ-ence has also been reported in Broca’sand Wernicke’s areas associated withspeech and language, and in frontalareas plausibly related to other behav-ioral traits including intelligence.11

The specific nature of morphologi-cal variability associated with the lo-cations of these functions is rather un-clear, even if they are geneticallylocalized. Do the heritable featuresspan sulcal boundaries? Are they inthe same place in each person? On thesurface or underlying it? We knowthat functions can re-map in the brain(e.g., in injured persons). While thereis a tendency to think of the cortex asbeing the seat of all function, it is ac-tually just a depot in many more dis-persed functional pathways. For ex-ample, visual function is accordedthree pathways, one via the thalamuson its way to the visual cortex in theoccipital lobe, one via the superiorcolliculus, the thalamus, the brain-stem, visual cortex, and frontal cortex,and a third via the pretectal brainstemand the thalamus. Combinations ofthese three pathways ensure actuallyseeing an object, locating it in space,and following it with your eyes.Though the cortex is involved, theother subcortical regions play equallyimportant roles in these pathways.Should we expect sulcal or gyral struc-tures to be tightly associated withthese functions?

It is not easy to infer from herita-bility studies what genes might beinvolved. A bit of light may be shedby a couple of experimental results.Over-expression of the �-cateningene in mice generated a sulcatedsurface, but the normal mouse brainis smooth,13 a finding interpreted asbeing relevant to functional (intelli-gence?) differences between mouseand human brains.14 Abnormal mu-tations in a gene called ASPM can beresponsible for greatly reducedbrain size and convolution complex-ity in humans.15

EARLIER VIEWS WELOVE TO HATE

In a broad evolutionary sense brainsize is correlated with function andwe’ve seen that human brain size vari-ation has been shown to have a ge-netic component. Still, Gould’s Mis-measure of Man16 is perhaps the best-known demonstration that brain sizehas been notoriously misused. He re-counts how the American anatomistE. Spitzka collected brains of the in-telligentsia and compared them withthe not-so. Spitzka and others at-tempted a size-based hierarchy fromAnimal to Man, but what they reallyfound was Animal to Anatole—Ana-tole France, that is, the small-mindedauthor who famously showed thatsize does not always matter.

To save the mental hierarchy in theGreat Chain of Braining, Spitzkaturned to convolutional complexity.As shown in Figure 5, it seemed obvi-ous that savage brains must be lesscomplex than those of great mathe-maticians. This drawing—if true—isinteresting because the other evidencewe’ve cited suggests that size is corre-lated with convolution complexity(whether by stuffing or billowing con-straints), and Gauss did not have aparticularly large brain. Given thecomplexities of relationships amongconvolution, size, and function, wecannot know if these diagrams wereaccurate for the specimens examinedor to what extent they were filteredthrough the sieve of their illustrator’sexpectations. Ideogram or fact?

These issues persist to the presentday. Investigators have combed (so tospeak) over Albert Einstein’s cadaver-ous brow on the assumption that hisbrain must have been different fromthat of us ordinary mortals.17 Usingassumptions about the tricks of Ein-stein’s trade (having to do with visuo-spatial reasoning), one somewhat en-larged area with enhanced sulcalcomplexity in a temporal lobe was in-deed claimed to have been found. Re-sponses to this necessarily post hocstudy of a sample of size 1 are highlyinstructive (The Lancet, 1999,354:1821–23), because the discussionis precisely about the kinds of featureswe’ve been discussing here. Can Ein-stein’s vast intellect be attributed tothis particular regional size enhance-

208 Evolutionary Anthropology CROTCHETS & QUIDDITIES

ment or sulcal length? Some portionof it? Anything visible at all, or just abiochemical difference? Or might itbe merely attributable to individualvariability that need not be related toa specific localized feature? My Syl-vian fissure’s bigger than your Sylvianfissure!

In 1798 Franz Josef Gall foundedthe science of phrenology. Phrenolo-gists mapped functional locations(Figure 6A), whose relative size theythought could be discerned eventhrough the skull. They were scientistsworking with what they had at thetime, but their idea that the furrows ofthe brow reveal the inner person is notconsidered scientific today because itdid not have what we consider ade-quate evidentiary criteria.

That was then. Today we insist in-stead on molecular furrows. We use so-phisticated electro-stimulation studiesin primates, observations of human pa-thology, and fMRI and PET imaging todemonstrate localized function in thebrain as in Figure 6B–C.18 This is a rep-licable kind of direct physiological re-sponse measure, but we’re too sophisti-cated today to think of trying to maptraits like an “imitation” area of thebrain (Figure 6A, arrow)—aren’t we?Well, that’s exactly what is done in Fig-ure 6B–C. By this modern test, the “im-itation” area curiously differs betweenleft and right sides on the surface, butdeep down, scanning shows “imitation”

to be right under where the phrenolo-gists said it was! What are we supposedto make of that?

There is humor here but this is notjust a joke. We’ve used this selectedexample not to defend phrenology,which clearly wandered into cultishnever-never land, but to ask that youre-read our earlier list of generally ac-cepted characteristics of the brain, in

the paragraph just before the “Sulciand gyri” section above. Those are thepremises with which Gall first articu-lated the science of phrenology, andphrenologists used data (of their time)and reasoning similar to what we usetoday (http://pages.britishlibrary.net/phrenology/other texts/retzer.htm).They established brain regions inrather post hoc ways, on small oppor-tunistic samples, and rationalizedcontrary or inconsistent observations.But we do that, too, and their idea wasnot different in principle from thestudy of Einstein’s brain—a seriousattempt published in the world’s lead-ing medical journal in 1999. Modernscanning methods permit greater ex-perimental control by real-time mon-itoring, and brain-mapping studies of-ten find variable and/or distributedrather than exceedingly focused maplocations in the brain. However, it isnot obvious how much more informa-tive or long-lasting these results willbe compared to past efforts. In anycase, they tell us little more about thenature of sulcal/gyral patterns per sethan a phrenology map could. This isespecially true given the amount ofinterperson variation, and the un-known degree to which functional lo-cation itself is really fixed.20

Figure 5. Spitzka’s convoluted reasoning (A) Papuan, (B) the famous mathematician K.F.Gauss (from16).

Figure 6. Phrenology old and new? Areas associated with the trait imitation by (A) the oldpalpable phrenology, (B, C) the new molecular kind (a PET scan), arrows indicate left andright superficial, and medial excitation areas for “imitation” test, respectively. (Source: A:public domain, relabeled for text readability; B, C.18)

CROTCHETS & QUIDDITIES Evolutionary Anthropology 209

LEFT BRAIN, RIGHT BRAIN

Genetic variation influences func-tional areas of the cortex, localizedbut with unclear relationship to gyralstructure. Genes may help account forcommon left-right asymmetries inbrain function—male and femalesides, spatial right, analytic left, andall that. However, both developmentaland genetic studies suggest that muchif not most of the observed variabilityis randomly generated. But does “ran-dom” mean not worth worrying aboutin diagrams of brain structure? That’srather subtle. We give high impor-tance to the human brain specificallyas having evolved to be flexible, notpre-programmed. Perhaps whatevolved was the means to produce therandom variation that we see in sulcalpatterns. Maybe that has the key func-tional implications for human cultureand behavior, much as the immunesystem has evolved specifically to gen-erate variation in disease response ca-pability.

If so, “stuffing” and chance is theright metaphor. That, rather thancoarser measures like size or multi-dimensional shape, may be what ex-plains the variation in musical or ath-letic ability, intelligence, andpersonality that capture so much at-tention. In such a view the relevantgenes might have to do with growthand timing, not specific functional at-tributes. This could be what the ASPMand �-catenin studies mean (if theymean anything), because these are in-tracellular spindle fiber, and generaltranscription factor genes, respec-tively, not, for example, neurotrans-mitter genes.

At best, current data show that it isnot so obvious what should be de-picted in a “scientific” drawing of thebrain surface, and the same issues ap-ply to other representations in sci-ence. What is the trait we want toportray, and how do we give the rightinformation? If some variation is ge-netic and other chance, and both can

have functional consequences in thesame brain region, how can we showthat? Indeed can we represent “the”brain, or just “a” brain? One recentpaper suggests that we should developa “probabilistic atlas” of the sulcal lo-cations,19 but that would be inher-ently sample-dependent. Perhapswhen art imitates life it conveys anerroneous sense of specificity. MaybeVesalius was more right to keep theconvolutions schematic than we are tobe more literal. These are not easyquestions to answer, and the reason isFleck’s: whatever our answer, it willembed within it judgments aboutwhat counts as a “fact” and who’scounting.

Our title is from Lord Byron’s once-popular poem Childe Harold’s Pilgrim-age. He used the wrinkled brow as ametaphor for “the worst of woes thatwait on age,” the passing of loved onesduring a person’s life. Here we askwhether it is the passing chanceevents in this life, or the accumulatedevents of ancestral ages, that stampedthe developmental wrinkles on ourbrow. As we have tried to indicate,whether this is a metaphorical or truebiological question is something toworry over.

NOTES

We welcome comments on this col-umn: kenweiss@psu.edu. Crotchety-Comments are maintained on: www.-anthro.psu.edu/rsrch/weiss lab.htm.We thank Anne Buchanan, Joan Rich-tsmeier, John Fleagle, and an anony-mous reader for helpful comments,and Jim Rilling, Tom Insel, PatrickBarta, and Godfrey Pearlson for theMR images.

REFERENCES

Many things discussed here can beprofitably explored by web searching.

1 Fleck L. 1935. Genesis and development of ascientific fact (1976 reprint, with editorial com-

ment by Kuhn and others). Chicago: Universityof Chicago Press.

2 Weiss KM. 2003. Come to me my melancholicbaby! Evolutionary Anthropol 12:3–6.

3 Vesalius A. 1543. De Humani corporis fabricaliborum, epitome. Basel: Oporinus (Copied fromDover reprint edition).

4 Singer C. 1952. Vesalius on the Human Brain.London: Oxford University Press.

5 Bartley AJ, Jones DW, Weinberger DR. 1997.Genetic variability of human brain size and cor-tical gyral patterns. Brain 120 (Pt 2):257–269.

6 Weiss KM. 2002. Good vibrations: the silentsymphony of life. Evolutionary Anthropol 11:176–182.

7 Lohmann G, von Cramon DY, Steinmetz H.1999. Sulcal variability of twins. Cereb Cortex9:754–763.

8 White T, Andreasen NC, Nopoulos P. 2002.Brain volumes and surface morphology inmonozygotic twins. Cereb Cortex 12:486–493.

9 Cheverud JM, Falk D, Vannier M, KonigsbergL, Helmkamp RC, Hildebolt C. 1990. Heritabilityof brain size and surface features in rhesus ma-caques (Macaca mulatta). J Hered 81:51–57.

10 Wright IC, Sham P, Murray RM, WeinbergerDR, Bullmore ET. 2002. Genetic contributions toregional variability in human brain structure:methods and preliminary results. Neuroimage 17:256–271.

11 Thompson PM, Cannon TD, Narr KL, van ErpT, Poutanen VP, Huttunen M, Lonnqvist J,Standertskjold-Nordenstam CG, Kaprio J,Khaledy M, Dail R, Zoumalan CI, Toga AW.2001. Genetic influences on brain structure. NatNeurosci 4:1253–1258.

12 Steinmetz H, Herzog A, Schlaug G, Huang Y,Jancke L. 1995. Brain (A) symmetry in monozy-gotic twins. Cereb Cortex 5:296–300.

13 Chen A, Walsh C. 2002. Regulation of cerebralcortical size by control of cell cycle exit in neuralprecursors. Science 297:365–369.

14 Vogel G. 2002. Development. Missized mu-tants help identify organ tailors. Science 297:328.

15 Bond J, Roberts E, Mochida GH, HampshireDJ, Scott S, Askham JM, Springell K, MahadevanM, Crow YJ, Markham AF, Walsh CA, Woods CG.2002. ASPM is a major determinant of cerebralcortical size. Nat Genet 32:316–320.

16 Gould SJ. 1981. The Mismeasure of Man. NewYork: Norton.

17 Witelson SF, Kigar DL, Harvey T. 1999. Theexceptional brain of Albert Einstein. Lancet 353:2149–2153.

18 Chaminade T, Meltzoff AN, Decety J. 2002.Does the end justify the means? A PET explora-tion of the mechanisms involved in human imi-tation. Neuroimage 15:318–328.

19 Chiavaras MM, LeGoualher G, Evans A, Pet-rides M. 2001. Three-dimensional probabilisticatlas of the human orbitofrontal sulci in stan-dardized stereotaxic space. Neuroimage 13:479–496.

20 Brett M, Johnsrude IS, Owen AM. 2002. Theproblem of functional localization in the humanbrain. Nat Rev Neurosci 3:243–249.

© 2003 Wiley-Liss, Inc.

210 Evolutionary Anthropology CROTCHETS & QUIDDITIES