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ELECTRICALSELF-STIMULATIONOFTHE
BRAIN
IN4
1
571
ROBERTC.HEATH,M.D.2’3
Atasymposiumconcerningdepthelec-trode
studiesin
animals
andmaninNewOrleansin1952,theTulaneinvestigatorsdescribed(and
illustrated
with
films
ofpa-
tientstreatedbetween1950-1952)apleas-
urable
responsewithstimulation
of
specificregions
ofthe
brain(5).
The
pleasurablere-
sponse
tostimulation
ofsomedeepregions
of‘thebrain,firstobserved
withelectrical
stimulation
tothe
septalregion,hasproved
aconsistent
finding
in
continuingstudies(6,
7,
12).Since1952wehavereported
various
aspectsofthephenomenonincludingdem-onstrationofreliefofphysicalpainbystim-ulationto
this
pleasure-yieldingareaofthebrain(11).Withthe
introductionofingenious
techniquesforself-stimulationbyOlds(14-17),theneedtodependlargelyuponverbal
reports
ofthesubjectiveresponsewaseliminatedanditwaspossibletostudyapparentrewardandaversiveareasofthe
brain
inanimals.Subjectivedata,ofcourse,werelackingintheanimalstudies.
During
thelastfewyearstheTulaneresearchershaveincorporatedandmodifiedsomeanimalintracranialself-stimulation(ICSS)
methods
for
humaninvestigation,permittingextensionofthe
pleasurable
phenomenonstudiesinman.AnICSSstudy
recentlypublished(3)
was
designedtoex-plorehumanbehavior
under
strictlabo-ratoryconditionsofthe
type
characteristic-allyemployedinanimalstudies.Astudyhasalsobeendescribedinwhichapatient
1Readatthe
119thannualmeeting
of
TheAmerican
PsychiatricAssociation,
St
Louis,
Mo.,
May
6-10,1963.
At
thetimeof
presentation,a
16
mm.
soundfilmwas
shown
demonstrating
the
effects
of
stimulation
bythetransistorizedportableself-stimulatortoanumberofspecificregionsofthebrain
in
PatientsNo.B-7andNo.
B-b.The
twosubjectswereinterviewedtoobtainsubjectivedescriptionsoftheeffectsofstimulation.SupportedbyfundsprovidedbytheLouisianaStateDepartmentofHospitals.2Dept.ofPsychiatryandNeurology,Tulane
University
SchoolofMedicine,NewOrleans,La.
3Charles
J.
Fontana,
Electroencephalographic
Technologist
and
Esther
Blount,
R.N.,Research
Nurse,Assistants.
wasequippedwithasmallportableself-
stimulatorwith
3buttons,permittingdeliv-ery
ofelectricalstimuli
of
fixedparameters
toanyoneof3brainsites(8).The
pri-mary
motivationinthesestudies,asinalldepthelectrodestudiesinmanatTulane,wastherapeutic(5).Studyofrewardareasinthe
brain
ofman,including
use
ofinducedrewardfortherapeuticpurposes,isextensiveandcom-plex.Thispresentationwillfocusonade-
scriptionofthesubjectiveresponses
oftwo
patients‘treatedbytheself-stimula-
tiontechnique.Theirreportsprovidein-formation
concerning
thereasonsforre-peated
ICSS-informationthatis
not
avail-
ablefromanimalstudies.
MATERIAL
ANDMETHODS
Twopatientswereusedinthe
study.
PatientNo.B-7,age28,withadiagnosisofnarcolepsyand
cataplexy,
had
failed
torespondtoconventionaltreatments.Hehadelectrodesimplantedbythemethoddevelopedinour
laboratory(
1,2)into14
predetermined
brainregionsandfixedto
remain
inexactpositionforprolonged
study.Thesesmallsilverballelectrodes
(mostofthoseusedinthis
studyconsisted
of3leadseachseparatedby2
mm.)were
placedintotherightanterior
andposterior
septalregion,leftanteriorandposterior
septalregion,rightanteriorhypothalamus,mid-linemesencephalictegmentum,
leftanteriorandposteriorhippocampus,
left
anterior
and
posterior
caudatenucleusandoverthe
right
frontal
cortex,right
andleftmid-temporalcortex,andleftan-teriortemporalcortex.
PatientNo.B-10,age25,apsychomotor
epileptic
with
episodicbriefperiods
ofim-
pulsivebehavioruncontrolled
withthe
usualtreatments,
had51leads
implanted
into17brainsites:leftandright
centro-
median,leftcaudatenucleus,
right
yen-tricle,leftandrighthippocampus,mid-
line
mesencephalictegmentum,leftand
right
septalregion,leftamygdaloidnucleus,leftparaolfactoryarea,andovertheleft
572
ELECTRICALSELF-STIMULATION
OFTHE
BRAININ
MAN
[December
andrighttemporal
cortex,
leftandright
occipitalcortex,
andleftand
rightfrontalcortex.
Twenty-four
leadswere
of
stainless
steel
.003
inchindiametercoatedwithTef-
lon;27
werethesmallsilverball
type
elec-trode.4ICSSstudieswerenotinitiateduntilaminimalperiodof6monthsfollowingop-eration,
assuringelimination
of
any
varia-blesintroducedbyoperativetrauma,
e.g.,
edema,anestheticeffects.
Stimuli
weredelivered
fromaspecially
constructed
transistorizedself-contained
unit5whichwaswornonthepatient’sbelt.The
unitgenerateda
pre-settrainofbi-directional
stimuluspulses
each
time
thatoneofthe3controlbuttonswasdepressed.Eachbuttondirectedthepulse
traintoa
differentelectrode
pair
permittingtheoper-ator
apossibleselectionofcerebralsites.Amechanicalcounterwascoupledtoeach
buttontorecordthe,totalnumberof
stimuli
directedtowardagivenarea.An
internaltimerlimitedeachpulsetrainto
0.5secondforeachdepression,therebyprohibitingtheoperatorfrom
obtainingcontinuousstimuli
merelybykeepingthebuttondepressed.Anadditionalfeatureoftheunitprovided3separatelevelpoten-tiometerstogivewide-rangecontrolof
stimuli
foreachelectrodepair.
Circuitdetaili.
To
minimize
theeffectsofdcpolarization,abi-directionalpulsewaschosen(Fig.1).This
pulse
per-mittedrestorationofthedcleveltozeroaftereach1.0millisecond
stimulus
andmaintenanceatzeroduringtheentiredead
time
of10
milliseconds.Asiliconunijunctiontimingcircuitgen-
eratedthebasic10millisecondinterval.
Theoutput
fromthe
unijunctiontransistorwas
gatedoffafter0.5secondoperationbyadiodegatedrivenfromanR-Gcharging
circuit.When
thediodegatewasopen,the
urnjunctiontransistorgeneratordrovetwocomplementaryone-shotmultivibrators
op-eratedserially,permittingthe
falling
edge
4
Stainless
steel
arrayconstructed
ofNo.
316stainless
steel
wire,
.003
inchin
diameter,
with
quadTeflon-coated
leads
and
6contactpoints2mm.apart.Electrodedesignedandfabricated
byHenry
A.
Schryver,110W.PackardSt.,Fort
Wayne,Indiana.
5
TechnicalAssociatesofNewOrleans.
FIGURE1
CircuitDiagramforTransistorizedIntracranial
Self-
stimulatorofthefirsttotriggerthesecond.Thetwomultivibratorshadequalperiodsof0.5millisecond.Themultivibrator
timing
cir-cuits
saturatedcomplementaryoutputtran-sistorswhichfedvoltagetotheloadthmugh
isolatingcapacitors.Thestimuliweremono-polar;thein-
differentpolewasaplatestrappedtothesubject’sleg.
Studiesconductedonthe
two
patientsdifferedsomewhatbecauseoftherapeuticconsiderations.
Forstudieswith
PatientNo.B-7,thenarcoleptic,the3buttonsofthe
unitwereattachedtoelectrodesin
theseptalregion,hippocampus,andmesen-cephalictegmentum,andhewasfreetostimulateanyofthesesitesashechose.Thepatientworethestimulatorforape-riodof17
weeks.
Beforehewasequipped
with
theunit,baselinedataconcerningthe
timehespentsleepingduringanarbitrary
6-hourperiodeachdaywerechartedbyspecifiedwardpersonnel.Thesedatawerelatercomparedwithsleeping
time
follow-
ingattachment
ofthe
unit.This
studywas
basicallytherapeutic(treatmentresultswill
bepresentedelsewhere)but
from
theex-perimentaldesignwewereable
toobtain
considerablesubjectivedataregardingtheeffectsofICSStoseveralregionsofthebrain.WithPatientNo.B-10,thepsychomotorepileptic,anumberofdifferentexperi-
mentaldesignswereemployedtoinvesti-gatetheeffectsofICSS.Forillustrative
purposes,theresultsofonestudyarepre-sentedhereinasbackgroundforadescrip-
FIGURE2
ComparativeSites,ICSS.FrequencyofStimulationto
VariousIntracranialSitesExpressed
InPercentagesIn
PatientwithNarcolepsyandCataplexy
Icss
ComparativeSites
tionofthesubjective
responses.
Inthefirst
part
ofthestudyatotalof17differentcerebralregionswerestimulated.Theywereselectedatrandom,the
unitdesignpermitting
3sitestobehookedupatanyonetime.Eachelectrodewasmadeavail-abletothepatientforstimulationfora
SSSSS
minimal
periodof2hours.Variouscom-binationsof3siteswerearranged.Thepur-
pose
inmakingstimulationtodifferent
combinations
ofsitesavailable
was
basedonwell-documented
animalstudies
whichindicatethatrateofstimulationatagivensitewill
varysomewhatdependinguponthesitestimulatedbeforehand.Dataarepresentedintermsofthehourlystimula-
tiontoagivensiteasrecordedwith
the
automaticcounterofthenull.Additionally,thesamesiteofthe
brain
was
attached
to
different
buttonstodetermineifthepa-tientwouldrelatearesponsetoagiven
button.
Hereported,however,aconsistent
response
tostimulationofagivenelectroderegardlessofthebuttontowhichitwasat-
tached.
Inthesecond
part
ofthestudythe3
sites
ofthebrainwhichthesubjecthadelectedtostimulatemostfrequently
during
thefirst
part
ofthe
study
werecomparedovera6-hourperiod.
80.
60
Septa
40
...,A
,
I1!
ntum
,
/\I!
20
\/
\
I
i
B#{149}7(P&W.)
\
‘‘
It1I
I
Weeks
lator,hewasemployedpart-time,whilewearingthe
unit,
asanentertainerinanightclub.Thepatient’snarcolepsywassevere.Hewouldmovefromanalertstateintoa
deep
sleepinthematterofasecond.Recogniz-ingthatbuttonpressingpromptlyawak-enedhim,fellowpatientsand
friendsoc-
casionallyresortedtopushingthebuttonifhefellasleepsorapidlythathewasun-abletostimulatehimself.Thepatient,inexplainingwhyhepressed
RESULTS
PatientNo.B-7.
Afterrandomlyexplor-
ingtheeffectsofstimulationwithpresses
ofeachofthe3buttons,PatientNo.B-7almost
exclusivelypressedtheseptalbut-ton(Fig.2).
Stimulation
tothemesencephalicteg-
mentumresulted
inapromptalerting,but
was
quiteaversive.
Thepatient,complain-
ingofintense
discomfort
and
looking
fear-
fiil,requestedthat
the
stimulusnotbere-
theseptalbuttonwithsuchfrequency,stated
that
thefeelingwas“good”;it
wasas
ifhewere
building
uptoa
sexual
or-gasm.Hereportedthathewasunableto
achievetheorgasticendpoint,however,
explainingthathisfrequent,
sometimes
frantic,
pushing
ofthebuttonwasanat-tempttoreachtheend
point.Thisfutileeffort
wasfrustratingattimesanddescribed
byhimon
theseoccasionsasa“nervousfeeling.”
PatientNo.B-JO.
Studiesconducted
on
peated.
To
makecertain
thatthe
region
wasnot
stimulated,heingeniouslymodi-
fleda
hairpin
tofitunderthebuttonwhich
directedapulsetrain
to
themesencephalictegmentum
soitcouldnotbedepressed.
Hippocampalstimulation
was
mildlyre-warding.Stimulation
tothe
septal
regionwasthe
mostrewarding
ofthestimulationsand,
additionally,italertedthe
patient,thereby
combatting
thenarcolepsy.By
virtueofhisabilityto
control
symptoms
withthestimu-thepsychomotorepilepticpatientwere
morevaried
andprovidedmore
informa-tionconcerning
subjectiveresponses.The
averagenumber
ofbuttonpressesperhourfor
variousregionsofthebrainislisted
in
Tables1and2.Regionsofthe
brainare
listedinorderofthefrequencywithwhichtheywereselectively
stimulated
bythesubject.A
summary
oftheprincipalsub-jectivefeelingsisgiven.
Thebuttonmostfrequentlypushedpro-
videdastimulustothecentromedianthala-
1963
1
ROBERTC.HEATH
573
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