ELECTRICAL SELF-STIMULATION OF THE BRAIN IN �4 1

571

ROBERT C. HEATH, M.D.2’3

At a symposium concerning depth elec-

trode studies in animals and man in NewOrleans in 1952, the Tulane investigatorsdescribed (and illustrated with films of pa-tients treated between 1950-1952) a pleas-urable response with stimulation of specific

regions of the brain(5). The pleasurable re-sponse to stimulation of some deep regionsof ‘the brain, first observed with electricalstimulation to the septal region, has proveda consistent finding in continuing studies(6,7, 12). Since 1952 we have reported various

aspects of the phenomenon including dem-onstration of relief of physical pain by stim-ulation to this pleasure-yielding area of thebrain(11).

With the introduction of ingenious

techniques for self-stimulation by Olds(14-17), the need to depend largely uponverbal reports of the subjective responsewas eliminated and it was possible to studyapparent reward and aversive areas of thebrain in animals. Subjective data, of course,were lacking in the animal studies.

During the last few years the Tulaneresearchers have incorporated and modifiedsome animal intracranial self-stimulation(ICSS) methods for human investigation,

permitting extension of the pleasurable

phenomenon studies in man. An ICSS studyrecently published(3) was designed to ex-plore human behavior under strict labo-ratory conditions of the type characteristic-ally employed in animal studies. A studyhas also been described in which a patient

1Read at the 119th annual meeting of TheAmerican Psychiatric Association, St Louis, Mo.,May 6-10, 1963.

At the time of presentation, a 16 mm. sound filmwas shown demonstrating the effects of stimulationby the transistorized portable self-stimulator to anumber of specific regions of the brain in PatientsNo. B-7 and No. B-b. The two subjects wereinterviewed to obtain subjective descriptions ofthe effects of stimulation.

Supported by funds provided by the LouisianaState Department of Hospitals.

2Dept. of Psychiatry and Neurology, TulaneUniversity School of Medicine, New Orleans, La.

3Charles J. Fontana, ElectroencephalographicTechnologist and Esther Blount, R.N., ResearchNurse, Assistants.

was equipped with a small portable self-stimulator with 3 buttons, permitting deliv-ery of electrical stimuli of fixed parametersto any one of 3 brain sites(8). The pri-

mary motivation in these studies, as in alldepth electrode studies in man at Tulane,was therapeutic(5).

Study of reward areas in the brain ofman, including use of induced reward fortherapeutic purposes, is extensive and com-plex. This presentation will focus on a de-scription of the subjective responsesof two patients ‘treated by the self-stimula-tion technique. Their reports provide in-formation concerning the reasons for re-peated ICSS-information that is not avail-able from animal studies.

MATERIAL AND METHODS

Two patients were used in the study.

Patient No. B-7, age 28, with a diagnosisof narcolepsy and cataplexy, had failed torespond to conventional treatments. Hehad electrodes implanted by the methoddeveloped in our laboratory( 1, 2) into 14predetermined brain regions and fixed toremain in exact position for prolongedstudy. These small silver ball electrodes

(most of those used in this study consistedof 3 leads each separated by 2 mm.) were

placed into the right anterior and posteriorseptal region, left anterior and posteriorseptal region, right anterior hypothalamus,mid-line mesencephalic tegmentum, leftanterior and posterior hippocampus, leftanterior and posterior caudate nucleusand over the right frontal cortex, rightand left mid-temporal cortex, and left an-terior temporal cortex.

Patient No. B-10, age 25, a psychomotorepileptic with episodic brief periods of im-pulsive behavior uncontrolled with theusual treatments, had 51 leads implanted

into 17 brain sites: left and right centro-median, left caudate nucleus, right yen-tricle, left and right hippocampus, mid-line mesencephalic tegmentum, left andright septal region, left amygdaloid nucleus,left paraolfactory area, and over the left

572 ELECTRICAL SELF-STIMULATION OF THE BRAIN IN MAN [December

and right temporal cortex, left and rightoccipital cortex, and left and right frontal

cortex. Twenty-four leads were of stainlesssteel .003 inch in diameter coated with Tef-lon; 27 were the small silver ball type elec-trode.4

ICSS studies were not initiated until aminimal period of 6 months following op-eration, assuring elimination of any varia-bles introduced by operative trauma, e.g.,edema, anesthetic effects.

Stimuli were delivered from a specially

constructed transistorized self-contained

unit5 which was worn on the patient’s belt.The unit generated a pre-set train of bi-directional stimulus pulses each time thatone of the 3 control buttons was depressed.Each button directed the pulse train to adifferent electrode pair permitting the oper-ator a possible selection of cerebral sites.

A mechanical counter was coupled to eachbutton to record the, total number ofstimuli directed toward a given area. Aninternal timer limited each pulse train to0.5 second for each depression, therebyprohibiting the operator from obtainingcontinuous stimuli merely by keeping thebutton depressed. An additional feature ofthe unit provided 3 separate level poten-tiometers to give wide-range control ofstimuli for each electrode pair.

Circuit detaili. To minimize the effectsof dc polarization, a bi-directional pulsewas chosen (Fig. 1). This pulse per-mitted restoration of the dc level to zeroafter each 1.0 millisecond stimulus andmaintenance at zero during the entire deadtime of 10 milliseconds.

A silicon unijunction timing circuit gen-erated the basic 10 millisecond interval.The output from the unijunction transistorwas gated off after 0.5 second operation bya diode gate driven from an R-G chargingcircuit. When the diode gate was open, theurnjunction transistor generator drove twocomplementary one-shot multivibrators op-erated serially, permitting the falling edge

4 Stainless steel array constructed of No. 316stainless steel wire, .003 inch in diameter, withquad Teflon-coated leads and 6 contact points2 mm. apart. Electrode designed and fabricatedby Henry A. Schryver, 110 W. Packard St., FortWayne, Indiana.

5 Technical Associates of New Orleans.

FIGURE 1

Circuit Diagram for Transistorized Intracranial Self-

stimulator

of the first to trigger the second. The twomultivibrators had equal periods of 0.5millisecond. The multivibrator timing cir-cuits saturated complementary output tran-sistors which fed voltage to the loadthmugh isolating capacitors.

The stimuli were mono-polar; the in-different pole was a plate strapped to the

subject’s leg.Studies conducted on the two patients

differed somewhat because of therapeuticconsiderations. For studies with Patient No.B-7, the narcoleptic, the 3 buttons of theunit were attached to electrodes in theseptal region, hippocampus, and mesen-cephalic tegmentum, and he was free tostimulate any of these sites as he chose.The patient wore the stimulator for a pe-riod of 17 weeks. Before he was equippedwith the unit, baseline data concerning thetime he spent sleeping during an arbitrary

6-hour period each day were charted byspecified ward personnel. These data werelater compared with sleeping time follow-ing attachment of the unit. This study wasbasically therapeutic (treatment results willbe presented elsewhere) but from the ex-perimental design we were able to obtainconsiderable subjective data regarding theeffects of ICSS to several regions of thebrain.

With Patient No. B-10, the psychomotorepileptic, a number of different experi-mental designs were employed to investi-gate the effects of ICSS. For illustrative

purposes, the results of one study are pre-sented herein as background for a descrip-

FIGURE 2

Comparative Sites, ICSS. Frequency of Stimulation toVarious Intracranial Sites Expressed In Percentages In

Patient with Narcolepsy and Cataplexy

IcssComparative Sites

tion of the subjective responses. In the firstpart of the study a total of 17 differentcerebral regions were stimulated. Theywere selected at random, the unit design

permitting 3 sites to be hooked up at anyone time. Each electrode was made avail-able to the patient for stimulation for a

�4 S S S S S

minimal period of 2 hours. Various com-binations of 3 sites were arranged. The pur-pose in making stimulation to differentcombinations of sites available was basedon well-documented animal studies whichindicate that rate of stimulation at a givensite will vary somewhat depending uponthe site stimulated beforehand. Data arepresented in terms of the hourly stimula-

tion to a given site as recorded with theautomatic counter of the null. Additionally,the same site of the brain was attached todifferent buttons to determine if the pa-tient would relate a response to a givenbutton. He reported, however, a consistentresponse to stimulation of a given electroderegardless of the button to which it was at-tached.

In the second part of the study the 3sites of the brain which the subject hadelected to stimulate most frequently duringthe first part of the study were comparedover a 6-hour period.

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lator, he was employed part-time, whilewearing the unit, as an entertainer in anight club.

The patient’s narcolepsy was severe. Hewould move from an alert state into a deepsleep in the matter of a second. Recogniz-ing that button pressing promptly awak-ened him, fellow patients and friends oc-casionally resorted to pushing the buttonif he fell asleep so rapidly that he was un-able to stimulate himself.

The patient, in explaining why he pressed

RESULTS

Patient No. B-7. After randomly explor-

ing the effects of stimulation with pressesof each of the 3 buttons, Patient No. B-7almost exclusively pressed the septal but-ton (Fig. 2).

Stimulation to the mesencephalic teg-mentum resulted in a prompt alerting, butwas quite aversive. The patient, complain-

ing of intense discomfort and looking fear-fiil, requested that the stimulus not be re-

the septal button with such frequency,stated that the feeling was “good”; it wasas if he were building up to a sexual or-gasm. He reported that he was unable toachieve the orgastic end point, however,

explaining that his frequent, sometimesfrantic, pushing of the button was an at-tempt to reach the end point. This futile

effort was frustrating at times and describedby him on these occasions as a “nervousfeeling.”

Patient No. B-JO. Studies conducted onpeated. To make certain that the regionwas not stimulated, he ingeniously modi-fled a hair pin to fit under the button whichdirected a pulse train to the mesencephalictegmentum so it could not be depressed.

Hippocampal stimulation was mildly re-warding.

Stimulation to the septal region was themost rewarding of the stimulations and,additionally, it alerted the patient, therebycombatting the narcolepsy. By virtue of hisability to control symptoms with the stimu-

the psychomotor epileptic patient weremore varied and provided more informa-tion concerning subjective responses. Theaverage number of button presses per hourfor various regions of the brain is listed inTables 1 and 2. Regions of the brain arelisted in order of the frequency with whichthey were selectively stimulated by thesubject. A summary of the principal sub-jective feelings is given.

The button most frequently pushed pro-vided a stimulus to the centromedian thala-

1963 1 ROBERT C. HEATH 573

574 ELECTRICAL S ELF-STIMULATION OF THE BRAIN IN MAN [December

TABLE 1ICSS in Man

Reward (?) Sites

lESION STIMULATED AVERAGE/HOUR SUBJECTIVE RESPONSE

L Centromedian 488.8 Partial memory recall; anger and frustrationR.P. Septal 394.9 “Feel great”; sexual thoughts; eliminationof “bad” thoughtsL Caudate 373.0 Cool taste; “likeitOK”Mesenceph. Teg. 280.0 “Drunk feeling”; “happy button”; elimination of “bad” thoughtsA. Amygdala 257.9 Indifferent feeling; somewhat pleasant, but feeling not intenseP. Amygdala 224.0 Moderately rewarding; increase of current requested

TABLE 2ICSS in Man

Aversive SiteS

REGION STIMULATED AVERAGE/HOUR SUBJECTIVE RESPONSE

R. Hippocampus 1.77 Stronglyaversive;“feelsick all over”L Paraolfactory 0.36 Moderately aversiveR. Parietal CortexR. Frontal Cortex

0.50 10.00 No significant subjective response

R. Occipital Cortex 0.00R. Temporal Cortex 0.00

mus. This stimulus did not, however, in-duce the most pleasurable response; infact, it induced irritability. The subject re-ported that he was almost able to recall a

memory during this stimulation, but hecould not quite grasp it. The frequent self-stimulations were an endeavor to bring thiselusive memory into clear focus.

The patient most consistently reportedpleasurable feelings with stimulation totwo electrodes in the septal region and onein the mesencephalic tegmentum. With thepleasurable response to septal stimuli, hefrequently produced associations in the

sexual area. Actual content varied con-siderably, but regardless of his baselineemotional state and the subject under dis-cussion in ‘the room, the stimulation wasaccompanied by the patient’s introductionof a sexual subject, usually with a broadgrin. When questioned about this, hewould say, “I don’t know why that cameto mind-I just happened to think of it.”The “happy feelings” with mesencephalicstimulation were not accompanied by sex-ual thoughts.

Patient No. B-10 also described as “good,”but somewhat less in pleasurable-yielding

quality, stimuli to two sites, the amygdaloidnucleus and the caudate nucleus. Several

other septal electrodes and one other elec-

trode in the amygdaloid nucleus were stim-ulated a moderate number of times. Hisreports concerning these stimulations sug-gested a lesser magnitude of pleasurable re-sponse, but definitely not an unpleasantfeeling.

Minimal positive response was obtainedwith stimulation of several other septalelectrodes. The most aversive response(“sick feeling”) was obtained with stimula-tion to one hippocampal electrode and onelead in the paraolfactory area. With stimu-lation of the latter lead, he complained oflight flashes, apparently due to spread tothe optic nerve, and of general discomfort.

No consistent changes, either significantlyaversive or rewarding, were displayed withstimulation to any of 12 cortical leads dis-persed widely over the cortical surface, in-cluding the frontal, temporal, occipital, andparietal lobes.

In the second part of the study the 3electrodes which were stimulated most dur-ing the first phase of the study were at-tached to the 3 buttons. The sites of theseelectrodes were the centromedian thalamus,the septal region, and the mesencephalictegmentum. Data indicated that the com-bination of sites available influenced the

19631 ROBERT C. HEATH 575

CSSComparison of Reward Sites

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number of times that a given region of thebrain was stimulated (Fig. 3). When cou-pled with the subjective reports, the dataalso suggested that the over-all state of the

subject at a given moment was an influen-tial determinant for selecting the region tobe stimulated. For example, the centro-median thalamus was stimulated up to1,100 times per hour when in combinationwith relatively inactive sites of stimulationand only a maximum of 290 times per hourwhen in combination with two other highlyrewarding areas, the septal region and themesencephalic tegmentum.

FIGURE 3Comparison of Frequency of Stimulation to Reward Sites

in the Brain of Patient with Psychomotor Epilepsy

The patient noted that the frustration andanger resulting from stimulation of thecentromedian thalamus was alleviated withstimulation to the septal region and to themesencephalic tegmentum. As Figure 3 in-dicates, ‘the patient during the first twohour’s stimulated the centromedian thalamusmost frequently. This was associated withdiscomfort in his attempt to recapture afleeting memory. He reported that stimula-tion of the other areas relieved this dis-comfort. There was little activity duringthe next two hours. Toward the end of thestudy, in the 5th and 6th hours, stimulationto septal and tegmental leads increased.During the 5th hour, the mesencephalictegmentum was stimulated most frequently;during the 6th hour, the septal lead wasstimulated most frequently. The patientevolved a pattern coupling the stimulus

to the centromedian thalamus (which

stirred his curiosity concerning the mem-ory) with stimuli to the more pleasurableareas to lessen the feeling of frustration.6

DISCUSSION

Changes in parameters of stimuli to agiven region of the brain, including cur-rent intensity, wave form, pulse width, and

frequency, in many instances altered thepatients’ responses. This has similarly beenreported with animal ICSS.

Information acquired from the patients’reporting of their reasons for button press-ing indicates that all ICSS is not solely for

pleasure. The highest rate of button press-ing occurred with Patient No. B-7 when hewas somewhat frustrated in his pleasurablepursuit and as he attempted to achieve anorgastic end point. In Patient No. B-10 thehighest rate of button pressing also oc-curred with frustration, but of a different

type, evolving with attempts to bring intofocus a vague memory that ICSS hadevoked. The subject’s emotional state inthis instance built into strong anger. It

was interesting that the patient would but-ton press to stimulate the region within thecentromedian thalamus for a prolongedperiod, but at a slower rate when buttonsproviding more pleasurable septal and teg-

mental stimulation were also available. De-pression of the septal button, with resultantpleasant feelings, alleviated the painful

6When the paper was presented, it was herethat the 16 mm. sound film was shown. Clinicaleffects of stimulation to a variety of deep regionsof the brain, as summarized herein, were demon-strated.

In the last sequence of the ifim, Patient No.B-10, the psychomotor epileptic, was stimulated inthe septal region during a period when he wasexhibiting agitated, violent psychotic behavior. Thestimulus was introduced without his knowledge.

Almost instantly his behavioral state changed fromone of disorganization, rage, and persecution toone of happiness and mild euphoria. He describedthe beginning of a sexual motive state. He wasunable, when questioned directly, to explain thesudden shift in his feelings and thoughts. This

sequence of film was presented to demonstrate aphenomenon which appears to be consistent andwhich has been repeated in a large number ofpatients in our laboratories. This phenomenon isthe ability to obliterate immediately painfulemergency emotional feelings in a human subjectthrough introduction of a pleasurable state byphysical or chemical techniques.

576 ELECTRICAL SELF-STIMULATION OF THE BRAIN IN MAN 1 December

- FIGURE 4Subcortical and Cortical Recordings from Patient withPsychomotor Epilepsy during Psychotic Episode. ThisRecord was Obtained During the Time that the Baselineof the Last Sequence of Film (Described Herein) wasTaken. Note the Predominant Spiking Localized Prin-cipally to the Septal Leads. This has Proved to be aConsistent Physiological Correlate with Psychotic Be-

havior

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emergency state, according to the subject’sreport, and thereby provided him comfortto pursue his quest for the fleeting memory.

With septal stimulation in other patients,as well as the two subjects discussed here,a sexual motive state has frequently beeninduced in association with the pleasurableresponse. This sexual state has not devel-oped in association with pleasurable feel-ings during stimulation to other regions.The consistent observation of a relation be-tween sexual feelings and stimulation tothe septal region has been described byMacLean in monkey experiments( 13).These reports, in part, answer questionsraised by Galambos regarding ICSS whenhe asked, “What motivates these animalsto do such unheard-of-things? Is it some

exquisite pleasure they receive, as severalstudents of the problem staunchly contend,or the feeling of utter and complete well-being as others claim ?“(4).

The ICSS techniques represent one ofseveral methodologies that the Tulane re-searchers have used in man to investigatethe pleasurable phenomenon associated

with certain types of cerebral activity.These studies complement early subcorticalelectrical stimulation studies(S). The pleas-

urable response has also been induced inman with introduction of certain chemicalsinto specific deep brain regions(8-10). Itis noteworthy that intense pleasurable re-sponses induced with chemical stimulationof the brain occurred when a high ampli-tude spindling type of recording was setup in the septal region (Figs. 6 and 7).

The observation that introduction of astimulus which induces pleasure immedi-ately eliminates painful emergency statesis quite consistent. if our psychodynamic

formulations are correct, ‘this basic observa-tion may have widespread implication forthe development of therapeutic methods toalter favorably disordered behavior.

Sur�t�i�y

Studies are described of two human pa-tients under treatment with ICSS. Theirsubjective reports in association with stimu-lation to reward areas of the brain are pre-sented. The data indicate that patients will

ROBERT C. HEATH

FIGURE 6Baseline Record of Epileptic Patient No. 65

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stimulate regions of the brain at a highfrequency for reasons other than to obtaina pleasurable response. These data extendinformation obtained from ICSS in animals.

BIBLIOGRAPHY

1. Becker, H. C., et al.: In: Studies inSchizophrenia. Cambridge: Harvard Univ.Press, 1954, p. 565.

2. Becker, H. C., et a!.: Electroenceph.Clin. Neurophysiol., 9: 533, 1957.

3. Bishop, M. P., et a!.: Science, 140: 394,1963.

4. Galambos, Robert: Fed. Proc., 20: 603,1961.

5. Heath, R. G., et at.: Studies in Schizo-phrenia. Cambridge: Harvard Univ. Press,1954, p. 42, 46, 47, 50,560.

6. Heath, R. C.: Psychosom. Med., 17:383, 1955.

7. Heath, R. C.: Confinia Neurol., 18:305, 1958.

8. Heath, R. C.: In Heath, R. C. (Ed.):

577

FIGURE 7Recording from Epileptic Patient No. B-5 FollowingInjection of Acetylcholine into the Sept31 Region

through lntracerebral Cannula

�

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Pleasure Integration and Behavior. New York:Hoeber. In press.

9. Heath, R. C., and deBalbian Verster, F.:Am. J. Psychiat., 117: 980, 1961.

10. Heath, R. C., and Founds, W. L.:Electroenceph. Clin. Neurophysiol., 12: 930,1960.

11. Heath, R. C., et a!.: In: Studies inSchizophrenia. Cambridge: Harvard Univ.Press, 1954, p. 555.

12. Heath, R. C., and Mickle, W. A.: InRamey, R. R., and O’Doherty, D. S. (Eds.):Electrical Studies on the Unanesthetized Brain.New York: Hoeber, 1960.

13. MacLean, P. D., et a!.: Trans. Am.Neurol. Ass., 84: 105, 1959.

14. Olds, J.: Physiol. Rev., 42: 554, 1962.15. _________ : Am. J. Physiol., 199: 965,

1960.16. Olds, J., and Mimer, P.: J. Comp. Phys-

iol. Psychol., 47: 419, 1954.17. Olds, J., and Olds, M. E.: In Heath,

R. C. (Ed.): Pleasure Integration and Be-havior. New York: Hoeber. In press.