Download On the Brain of a Scientist: Albert Einstein

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On the Brainof a Scientist:AlbertEinstein
M a RreN C . D IntroN n,* A R N oLD B . S cH erarl ,f
G n e e R M. MuR pH y, Jn.,t aN n TH ouas H nR veyr
'Departments of Physiology'-Anatomy and {,4nthropology, tJnitersitl, of Catdornia, Berkelev,
California 94720, and lDepartnents of Anatomy and psvchiarry, Ltniversitl, of
Caldornia, Los Angeles, Caldornia 90024
Received Seprember 25, 1984
Neuron:glial ratios were determined in specificregions of Albert Einstein's cerebral
cortex to compare with samples from I I human male cortices. cell counrs were
made on either 6- or 20-pm sections from areas 9 and 39 from each hemisphere.
All sectionswere stained with the Kliiver-Barrera stain to differentiate neurons from
glia' both astrocytes and oliogdendrocytes. Cell coun6 were made under
oil immenion
from the crown of the gyrus to the white matter by foilowing a red line drawn
on
the coverslip. The average number of neurons and glial cells was delermined per
microscopic field. The results ofthe analysissuggestthat in left area J9. the neuronal:
g lia l r a tio fo r th e E i nstei n brai n i s si gni fi cantl ysmal l er than the mean for
the conrrol
p o p u la tio n ( r = 2.62, df 9, p < 0.05, tw o-tai l ed). E i nstei n's brai n di d not
di ffer
sig n ih ca n r lyin th e neuronal :$i al rati o from the control s i n any of the other rhree
areasstudied. c) t98i Academrc
pre$.Inc.
INTRODUCTION
Albert Einstein is generally conceded to have had one of the greatest
scientific minds that ever existed. whereas neuroscientistsmay have no
idea what characterizedthe brains of an Aristotle, Galileo, or Newton aside
from the extraordinary quality and prodigous quantity of their work, we
are fortunate when we turn to a consideration of Einstein. we recently had
the privilege of access to sufficient tissue from Einstein's brain to make
certain quantitative measures. Becauseof the method used for preparing
the tissue for histological examination, we were limited in the kind of
analysiswe could make.
r Ap p r e cia tio n is e xte nded
to R uth E . Johnson and E . R osal i eGreer, ph.D , l or therr excel l cnt
technical assislanceand to Doug Coe for his editorial critique. Dr. Harvey's current
address is
Wcsto n , M O 6 4 0 9 8 .
198
0014- 4886/ 85
$3. 00
Cop!n8ht !c, 1985 by Acadcmic Press.Inc.
{ll nghLsdl rrproduclron rn anv form re*ned
E IN S TE IN 'S B R A IN
C E LLS
19 9
T h e F re n c h m athemati ci an,
JacquesH adamard, w as i nterested
i n deter _
m i n i n g rh e n a ru reof rhe
menrai ;;;;f
marhemari ci ans.
-mentar--images
H e conducred
a psychorogicarsurvey
of the
or internar words which
ma th e ma ti c i a n suse ,
..w hether
they
ob'H;;;;;'J''l'ili''X'li?l'.
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Here
rt,n", "'.","1,i::
",
#;'"?
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?J:['l,JTITT:'.'..":i
.rr"ntiuri*i" r., producrivethough :f :ti
t. Einsrei
n
#tT:; ;::H."J:r:.,r.
" logicaily
t:
finallv .i
"at
.onn..lJ conceprs
wasrhe emotionar0""1"":]:t
i,-ve
slsol a rather
vagueplay of visuaiand ,o-.
types',(10).
-rr.utu.
It is doubtful whetherany singre
region
modal interactions-When studyi;;;i;;Jr,s of the brain mediatesa, cross
brain, *" i;;;;;..,...rru.,
to chooseregions *rr:h seemed";;-'"f;;*.the
read provided by his
rntrospection'we decided-to
examin" .orti.ur association
regionsof the
superiorprefrontal and inferior
spheres.Neuronal:gtialrarios o".i.i"r'iri.s in the rigrt and reft hemi_
i" ,1.r. *.";;:.:"ii'":,,:fl
::: representing
],
as
onevarid
-.uru..-oilhe
'
srarus
"rr*r"r"r
ffi:ff'ilj:ted
'l
METHODS .
A controrbaseof marehuman
brainshad,beenobtained
duringthe last
few yearsfrom the Vereran's
ea-i"lt"lii*
Hospirarin Martinez,California.
Theseincrudedr r brains
non,'inoiuiJurr, o, ,o g0 years
of agewho had
died from nonneurorogicattv
.etatJ otr."ril tn"
64 years;
trrn r J."irll'rc,i,o
"*."*.;;:,
norogica
r
"
"r'ff:;ll ;:: J:":,, :,
nIy
"r1r,-,"i I ecessa
""
arsopray",i;;;;;if :ltr,ff l"t?'":'J:,X
,._11
..;"":
*i'', i'u-in''J"i n' i :ru:::rm,_
ff#:fi:.t5}'J"*fl 'J;
-'
sthat,n.,
lo notcome
From the Formarin-fixed
brains-of former vA Hospital
-r.-oued
patients, brocks
of cerebrar cortex about r
.25 cm2 *.r.
from
g (superior
area
fronrar gyrus on
,ur"ro..) uno area 3g (inferior
'n"..^oi:u'.ru,.*i
parietai
it, "'",".ev "." ding,he
il,:x'
:
r
?,'
:'
:T
il:
l
#;;j,
"-"
: from -,,
ii*
both right
hemispheres
and left
G.;;t:
r). The brocks*...,tut'
rhesurrace
u'po,,ifri.
;Ji;:,;l"j:#fff;ild;.J3;,I:
.d*prv
Of
groupofll9
I I brains."no*i
n.r.i
Iralrc:. .rhis
rrom
8 brai
nsa"nd
.lrroioin
*.,i""r'"il
,.
;'H: ffi ::: [TJ:T'::::
The Einsteinbrain blocksf.orn
.
u..u, 6'l
h
emisph
eres
j;0.;1J:::,,1.
i rheraboraroo
".i ".J'were
" taken non' ;,.;"
micrometer sections
.:fi::.il: J;:
einst.rn,s
brain. Four to six secrions
,j
lrl
ltl
lri
J"
I
I
.4
I
;i
200
lf
DIAIVION D E T A L,
f
Frc. l. A lateral view of the human brain indicating the position of the samples removed
for cell counls. A representsthe sample from area 9 and B, area 39.
were cut from each block, Einstein's and the controls'. All brain sections
were stained with the Kliiver-Barrera, luxol fast blue cresyl echt violet
stain, to differentiate neurons from glia. After staining, one of the six
sectionsfrom each block was chosen for study. To assure the vertical
orientationof the cell counts, a straight line, perpendicularto the crown of
the gyrus, was drawn with a red pen on the coverslip. This ruled line was
kept just out of the field of vision as the cell counts were made, beginning
at layer II and extending into the subcorticalwhite matter. Cell counts were
m ade w i th th e a i d o f a n o i l i m m e r si on l ens (100X ) and an eyepi ece(l 0X ),
with a ruled graticule placed in the eyepiece.
Since the demarkation between cortical gray matter and the underlying
white is not as clear in the human brain as in the rodent brain (3, 5), the
number of microscopic fields sampled was more arbitrary. Counts were
made into the white-gray boundary for one or two fields dependingon the
density of the myelinated fibers, which are clearly demonstratedwith this
stain. Two vertical columns were counted in the brain sections and the
averagenumber of both neurons and glial cells per microscopic held was
if
flr
$
ff
f
determined.
fl
it
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il
t
fl
xl
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E IN S TE IN 'S B R .\IN C E LLS
201
T h e c o u n tswere made i n the fol row i ngmanner: B egi nni ng
at the j uncti on
of layer I with layer II, the purple-stainedneurons with
crearry defined
nuclei and nucleoli wer_ecounted in a singremicroscopic
field. The position
of each neuron in the fierd was marked on a ruled sheet paper
of
identical
in formar to the grid within the eyepiece.In this way
the invesiigatorcould
be certain which neurons were tabulated thereby preventing
oversight or
duplication.
Two types of glia fulfilling a standard criterion were
counted: astrocy.tes
with large, clear, brue-stainednuclei and origodendrocytes
with smailer,
deeply stained, blue nuclei. visual differentiation of
astrogliarnuclei from
those of small neurons is a frequently cited problerq in
neuiocytologic work
of this type. Previous studies attest to the effectiveness
of creil echt violet
in distinguishing between these ceil types (6, g). The grial
counts were
recorded on the same sheets as were the neurons.
To determine the
neuronal:glial ratios, the counts of the astrocy.tesand
oligodendrocyreswere
pooled from each section to provide a singre gJiat
count. In addition,
neuronal:astrocytic and neuronal:oligodendrocytic ratios were
calculated.
shrinkage factors for frozen sections versus celloidin sections
have been
considered in previous studies where we rearned that
our experimental
differences between groups were the same whether we
used ceiloidin or
frozen sections (3).
l
il t .
rii
4i:,
RESULTS
To test whether the Einstein brain diflered significantly from the popuration
from which the l l control brains were sampled,the mean and
the standard
deviation for the sample were taken as estimatesof the population parameters
1t and o. Then, the deviation of the neuronal:glialratio for Einsrern'sbrain
from the mean neuronal:glialratio for the sample was computed
in standard
deviation units. This score was referred to a Student's t distribution
with
nine degrees of freedom, because two degrees of freedom
were lost in
estimation, one for the mean and one for the standard
deviation. The
resultsof this analysissuggestedthat in left area 39, the neuronal;gjial
ratio
for the Einstein brain was significantly smailer than the
mean for the
control population (t = 2.62, df g, p < 0.05, two_tailed).Einstein,s
brain
did not.differ significantryin the neuronar:grialratio from
the contrors in
any of the other three areasstudied (seeTable I ).
Neither the neuronar:astrocyicnor the neuronar:oligodendrocy,tic
ratios
by themselves were significantry different in any
oi tte ur.", ,,ud,.d,
comparing Einstein'sbrain with the contror brains. It was
necessaryto pool
all glial cells counted to attain statisticailysignificant
differcnces,but the
data indicated that one gliar celr type arone *as not
responsiblefbr the
differencenoted.
202
D I A ] V I O N DE T A L .
TABLE I
Neuron:Glial
RatiosbelweenEinstein's
Brainand Thoseliom ll lVtales
(47 to g0 yearsof Age)
Rcg io n
Left area 9
Rig h t a r e a 9
Left area 39
Rig h t a r e a 3 9
N:Gi
( l I mal es)
SD
1. 8 4 9
1. 75 4
t.936
2.026
0.661
0.755
0.312
0.588
N :G;"
E i nsrei n
L04
l, l6
l .t2
0.92
VoL
77
5l
73
t20
NS
NS
0.05
NS
' ln e ve r ya r e a Ein ste inh a d a smauer N :G rati o, but by compari ng
one brai n rvi th t l havi ng
relatively rargeSDs, the resurtsshowed only one area to
be significantry different.
DISCUSSION
we studied the prefrontar and inferior parietal
association areas of
Einstein's brain because such areas are known
to be concerned with
"higher" neural functions. These regions do
not directly receive primary
sensory information, but rather, as their name implies, ,.associate,,
or.
analyze inputs from other brain regions. The associaiion-cortices
are the
last domains of the cortex to myerinate, indicating
their comparatruety rate
development. It is not possible at present to identify
with a t igi oegree of
specificitythe independent functions of these ,on"r.
Charactenzing the
modes of function of the corticar associationregions
may prove to be one
of the most elusiveof all neurobiologicaltasks.
considering the fact that the tissue blocks were
already embedded in
c_elloidin
when they becameavairablefor histologicarstudy (thereby
making
Golgi or other more revearingstudiesimpossibre),we
decided that differential
cell counts constituted a potentiaily meaningfur measure
of the functional
statusof the brain. Not only is the cerebralcortex
rich in its distribution of
nerve cell bodies,but grial ceil types arso constitute
a large fraction of the
mammarian cerebral cortex. Bass e/ at. (2) reported
thlt neu.onar:griar
ratios decreaseas the phylogeneticscale is ascended
from mouse to man.
on the other hand, Rocker et at. (r6) demonstrated
remarkabreconsistencv
in the absolute number of nerve ceils in cortical
strips from pi"r ,".r*"'i"
white matter, regardressof the mammalian
speciesor cortical thickness.
Such uniformity in number was found, for instance
in the motor cortex
(area 4) and in the somatosensorycortex (area
3b), arthough not in the
visual cortex (area l7) which has about two-and-one-half
times as many
neuronsas other cortical areas.
The thicker corticesof large mammals seemsto
be primarily a function
of largenerve cell bodies,more extensivedendritic
and axonal systems,and
concomitantly, more numerous glial cells. Furthermore,
environmentar
E IN S TE IN 'S B R A IN C E LLS
203
ennchment and other augmentedneural inputs
in the rat increaseall these
neuronal measuresof enhanced cell activiiy
together *i,r.,
rncreasein
th e n u mb e r o f g J i a lcel l s(l , 3, 5,7, g, I l ).
""
An increasein the number of gJialcets without
a significant increasein
the neuronal population suggests
a responseby gJialcellsto g..ot.. neuronal
metabolic need. Alr thesedata suggestthat
neuronar;gJiar
ratios in serected
regions of Einstein's brain might reflect
the enhanced use of this tissue in
the expressionof his unusuarconceptuarpowers
in compariso, *i,;;;;,r;;
brains.
The rationaie for choosing the prefrontal
and infraparietal regions was
basedon the specurationsof severalinvestigators.
co-p-oi*"
anatomicar
studies indicate that
parietal lobe expand, progr.rriuely
to
crowd the
motor, auditory, and-the
visual cortices forward, downward,
and backward,
respectively'studies,of.endocastsby von
Bonin (17) comparing panetal
and frontal lobes led him to conclude that
it was this exiansion of the
parietar lobe which was most characteristic
of the human brain. According
to Passingham(15),-on the other hand, the prefrontal
cortex is thought to
subservein unique fashion those activities
and quarities which distinguish
man from other mammals and primates. The
anterior portion-ortire frontal
lobe appears to be engagedin the temporar
organization oit"iuuio.,
..g.,
the planning and estabrishment of behivioral
itrategies (t3). From tesion
studiesin animals and human beings,it has
been sho*n thaitheprefrontal
cortex is involved in mechanismsof attention,
recent memory, capacityfor
abstractingand categorizinginformation, and
the formuration and initiation
of actions- The parietal robe has been associated
with tr,e in-t-egrationot
visual,auditory and tactile modalitities
and with problems of self-lwareness,
imagery, memory, and,attention (r4). Lesions
in the inferior parietal region
(area 39), especia,y of the dominant
side, resurt in inabirity io read words
or letters, and in gross impairment in writing,
spering, aJ catcutation
[(12), for recent review see(9)].
one mathematician with a resionin area
39 found it difficult to draw or
write formurae and courd not use a slide rure.
Howev.., u, nigii he could
visualizethe correct construction of the formulae
(3). A mathematician at
the University of California, Berkeley, calvin
Moore, ,,ur.o ,r,u, tr. d.u"lop,
a feeling of reality for abstract concepts. They
exist in his brain and can be
manipulated like real objects. It is the interpray
of these obj;
*r,i.h
contribute to mathematicar insight. It has
also been .eporteJ ,n"i"i""in;
-uu
educatedindividuar, resionsin the inferior parietal
robule of the dominant
hemisphereresult in the loss of versatility
oi i-ug.ry and the capabilify for
c o m p l e x th i n k i n g (3 ).
The possibrerelationship of these phenomena
to Einstein,s inte'ectual
gifts served as a guide for the selection
of our tissue samples.It therefore
seemedconceivablethat area g of the prefrontal
cortex and/or area 3g of
20.1
DI r \ N t O N D
and/or nght sidesmight be charecterized
the inlerior panetalcortexon rhe left
ratlos'
by smaller than normal neuronal:g-lial
ratio in area 39 of the left
neuronal:glial
the
Our data suggestthat
glnsteinlsbrain is significantlylower than that of the control
hemispherein
(e'g''
which measurementswere made
subjects,or of the other regions in
ar ea 3 g ,ri g h t:a re a c ,te fta n a ri g h t).Mental acti vi ti esascri bedtoarea39
himself made about his conceptual
fit many of the comments that Einstein
processes.
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I
1l
I