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Dear Dr.

While I'm not entirely settled in as yet, and am currently losing a stiff fight with a heavy cold, I am in residence, and we might plan another conversation so as to firm up our interests.

As you kncw, I spent about three years working in the research area of rewarding electrical stimulation of the brain - the "Olds effect," as it has sometimes been called. The work that we did involved both basic and applied aspects. In the laboratory, we performed a number of experiments with rats; in the open field, we employed dogs of several breeds. The culmination of our work was several publications that elucidated the nature of brain-stimulation reward, in addition to a demonstrated procedure for controlling the free-field behaviors of an unrestrained dog. Behavioral control was limited to distances of l00 to 200 yards, at most. Both kinds of work were described in detail in the final report for that project (Contract which, I believe, you have in your possession.

It was clear to me on the basis of our earlier talk that some of the work thit we did was closely related to your current interests, although I must confess that that conversation was sufficiently nondirective that I came away with no clear idea of your precise research needs at the moment. Accorjingly, the following are some thoughts regarding what we might be ableto do.

We could establish an "under the roof" laboratory that would be equipped to study the basic parameters of the control procedure using a small animal such as the rat. I have in mind the construction of a sizable enclosure, a miniature representation of an open terrain. Basic experiments can be performed in that setting, once the job (and I think that it might be a difficult one) of objectifying the recording

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of the open field behavior is accomplished. An interesting possibility would be the development of an automated control procedure, i.e., instead of guiding the animal continuously by hand from point A to point B, the animal is guided by means of an automatic direction system. I can't imagine how this system might work, however. It does seem to be primarily an engineering task, rather than a problem in behavioral research.

On the other hand, you might be more irmediately concerned with more practical matters and wish to forego problems in basic research, i.e., rat work. Work in the open field could employ a range of species; ve've used dogs before, but I think that the same procedures could be employed with other species. A problem arises in that electrode implantation may be difficult if adequate atlases are unavailable. I don't know offhand the species for which stereotaxic atlases are available. Clearly the auto-. matic guidance system that I mentioned above would be useful here. Again, I think that the problem is an engineering problem, since I can already specify the behavioral requirements of the system, but I can't specify the hardware.

There are behavioral problems that can be researched, however. If a small animal is to move from point A to point B. automatically controlled or under constant control by a human, what problems of competing rewards do we face? How easily is the animal distracted and by what? If control is lost, how may it be reestablished?

One of the problems with working with dogs is the absence of a suitable open field nean. ldoes own about 75 acres in fand a facility, perhaps including surgery and laboratory, could be established for-the purpose. It's likely to be expensive, however.

I really don't know what else to say at this point, which is why it's been so difficult to get this letter written. If you can suggest specifically the kinds of problems that interest you, perhaps I can Łe more constructive. I'll be locking forward to seeing you on 10 October.

Sincerely,

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ABSTRACT

1.

2. Title of Report: Remote control of bchavior with rewarding electrical stimulation of the brain.

3. Principal Investigator:

h. 69 pages, 8 figures, 30 Septemter 1965.

5. Contract number:

6. Supported by:.

This is a final report, and the results of our vork are sumtarized. The specific aim of the research program vas to examine the feasibility of cortrolling the behavior of a dog, in an open field, by means of remotely triggered electrical stimulation of the brain. The report describes such a system which depends for its effectiveness on two properties of electrical stimulation delivered to certain deep lying structures of the dog brain: the well-known revard effect, and a tendency for such stimulation to initiate and maintain loconotion in a direction vhich is acconpanied by the. continued delivery of stimuletion. Experimente on the parameters of stimulation are described, in addition to an experiment on the ability of a conventional reinforcer, food, to disrupt ongoing, free field behavior under the control of rewarding brain stipulation. Finally, supporting research employing albino rats is swmnarized.

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Y: Pone
I. Aims..
1
A. Speciric
1
B. General
2
II. Facilities .....
3
III. Research Activities .......
4
A. Work related to specific goals of the contract... h
B. Sume and Conclusions . 30
C. Supporting research ......... 31
D. Additional research . 46
IV. Applications ......... 62
V. Publications ..... 65
VI. Papers read at meetings .............. 67
VII. Previous reports in this series .............. 68
VIII. Distribution list ....... 69

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TABLE Of FIGURES

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FINAL REFORT

· I. Aims

The aimo of our work over the past three years were specific with respect to some research problems and general with respect to others.

A. Specific

Since 195h, it has been known that electrical stinulation of certain deep lying structures in the brain could serve as an instrumentalreinforcer, 1.e., a reward in the sense that an organism vould perform some specific behavior which produced or was folloved by such stimulation. It vas known, further.. that. the effect could be obtained in several species of laboratory animal: rat, cat, monkey, guines pig. Research work centered on detcrmining specific loci and systems in the brain which produced reverd effects upon stimulation; determining interactions emong systems, perticularly those maintaining revarded and escape behaviors; developing an integreted, conceptual account of meny, findings on revarding electrical stimulation of the brain.

It is not dirficult to conceive of some practical applications of reinforcing brain stimulation. The work uncertaken in these laboratories vas concerned vith the exploration and development of ore such application, i.e.. the control of open field behavior by revarding brein stimulation triggered fron a point remcte from the behaving organism. The experi-

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: mental aninel choeen for thio vork vas the dog, and that choice

1. A stereotaxic atlas of the dog brain vas available and an electrode placement providing reliable reward effects upon stimulation bad to be located. 2. A sall, portable stimulator which could be atteched to a dog harness and connected to its electrodes ves needed. The stimulator had to be reliable and capable of sufficient voltage output to be usable in the face of expected
impedance variation across individuel dogs. e 3. The precise method of controlling open field behavior had to be determined. 'The control of free-field bebavior may be conceptualized, in general, as moving the dog from one arbitrary point in the field to any other arbitrary point. There are potentially a pumber of procedures vhereby this mey be accomplished, ranging from the stimulus control of discrete movements to "homing on a beem."
4. Given s-lutions to the above questions, the peraneters or the control technique should be explored. The degree of distractability of a dog actively under control is a
question of importance with regard to any potential Bpplication of the control system.

B. Ceneral

Subsidiary to the specific sims of tha contract reseerch,

ve undertook to explore some geceral questions regarding the

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nature of rewerdirg electrical etimuletion of the brain. Much of this reseerch vas performcd with the albino rat as the experimental subject.

1. There have been suggestions in the research literature that brain stixulation as a reinforcer may have properties different from conventional reinforcers such as food and water. We undertook to explore this question, with particular emphasis on the ability of revarding brain stimulation to maintair in strength perfornances of an order of cooplexity equal to those maintained by cooventional reinforcers. A satisfactory solution to this probiem bad relevance to the field vork vitb the dog.

2. Experizents reported in the literature vhich deal with comparisons between revarding brain stimulation and the conventional reinforcers are, in our opinion, unsatisfactor in that the baseline performances for the two reinforcers heve not been equated. We undertcok to develop an experimental procedure which vould permit not only the eçuetion of the performances maiatained by the tvo reinforcers, but also permit an inequality defined and controlled by the experimenter.

II. Facilities

The several pheses of the contract vork were housed in a nev repearch building The building, 3oo0 sq. rt. under the roof, provided office space, an electronics shop, rooms for prograuming equipnent, separate roons

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for experinental animel chonbers, anical holiing facilities for several species, and a surgery. Histology facilities, mainteined in another building, vere provided
were generously avellable to us. Machine shop facilities vere also available.

Finally, our main Laboratory building vas located in a relatively secluded area on a fenced plot of land one acre in size. Those accomodetions permitted the private conduct of field vork. The above facilities became available in the early summer of 1963.

III. Research Activities

The research activities undertaken during the term of the contract mey be divided conveniently into: research directly releted to the specific goals of the contract, and supporting research. Substantial portions of both research efforts have been described in detail in previous reports. When it is necessary to refer to those espects of our vork, ve will do so briefly and reference the previous report in which deteils may be found.

A. Work Related to Specific Coals of the Contract.

1. Electrode placement in the dog.

The vork on electrode plecement begen when ve entered
the new research buildine that vas provided 1 Initial electrode placements that
we examined proved to be unsatisfectory in that lever
pressing could pot be maintained in a lever-press dog box.
The dirricultizs encountered vere described in our report

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of 1 January 196h. In addition, it became apparent, at thet time that the electrode preparation itselr offered some special problems vith a dog that are not ordinarily faced with the ret as an experimental subject. Those problezs vere (a) protecting the electrode from damage, and (b)
infection at the electrode site due to a failure of the C
surgicel vound toheal. The plaatic belmet that vas devised to protect the electrode from damage vas described in our report or 1 Jenuery 1964. A better technique that ve
developed involves exbedding the electrode, entirely vithin : a mound of dental cement on the skull and running the leads subcutaneoualy to a point between the shoulder blades of the dog vhere the leads are brought to.the surface and arfixed to a standard dog barness. The newest procedure vas
described in our report of 1 Jaouary 196s, and it continues to be perfectly satisfactory in terms of durability
(measured in mooths) of the electrode assembly and
protection from infection, since the skin is closed entirely over the electrode site..

The electrode placenents that we heve employed subsequent to our earliest attempts have been satisfactory, and ve bave complete confidence in our ability to surgically produce a dog that vill show strong revard effects in a lever pressing box and in the field. Pigure 0 shows brain sections obtained from several of those dogs. The heavy, derk markers locate the electrode tips. The medial mammillary

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Pigure 0

Sample histologicel sections shoving typical electrode plecements producing revard efrecta in the dog.

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bodies of the posterior hypothalamus are evident in sections B and D. Placemcntg in that region are known to be anong the best in prosucing reverd effects in rats. In sections A, B, and D, the electrode tips ere in the Campi Foreli; in section C, the Medial Lenniscus, leteral to the Red Nucleus. $\bullet _ { \bullet }$

The subatantiel response rates in the lever-press box obtained with stimulation in the regione Juet defined vas stated in our report of 1 January l964. Subsequent to that report, ve have performed experiments in which lever pressing could be maintained on scbedulee of intermittent revard in. the dog. Fixed ratios in excess of 100 responses per reward vere easily obtained.

2. The portoble atimuletor emerged as a major problem. We etterpted construction of a small, remotely triggered stimulator in our own laboratory-- problems of minia-. turization vere soon encountered, and the engineering problem was undertaken by the

ment vas delivered in October, l963, but it never functioned satisfactorily. A series of reports, written by described the bistory of our reletionsbip and the perforwance of the stimulstor. The reports vere submitted to the

mation purposes. As described in our report of 1 Januory 1965, ve turned to

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for the commercial development of the portoble, remote controlled receiver-stimulator and transmitter units. Through . a local representative of 1

the unit vas designed, completed, and delivered to us early in 1964. Some modification to the basic instrument vas necessary, and subsequent to those modiricatiors, the unit bas performed in a completely satisfactory manner. In terms or size, it is easily atteched to an ordinary dor harness; in teras of veight, there is no interference with the dog's norzal gait. The unit delivers a l00 cps sine-vave at an adjustable voltage. maximum: 50v peak-to-peak.

3. Prior to tbe delivery of the portable stioulator, ve undertook fleld vork employing a "direct-line" system, i.e... the dog ves connected to a stimulator, located in the laboratory, by means of a cable suspended over a smell, fenced enclosure. Our report of 1 January 196s describcd the reseerch, In summary, ve developed two techniques for the control of e dog's behavior in' the smell enclosure. .The firet involved the elicitation of movements such as runningi turning, stopping, ete. When produced in an appropriate sequence, a dog could be moved from one point in the enclosure to another. There are several disadventages to the "elicited-behavior" metbod-- several electrodes, each producing oze of the required movements, are necessars in each dog. Although implanting the several electrodes 1s no

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special probles, ene is never certain which elicited movements vill be obtained fron each of the electrodes until stimulation 1s attempted. Thus, there moy nct be a suitable combination of novements in a particular dog. Secondly, the stimulation intensities required'to produce elicited movements are relatively bigh-- bigher than ve cen obtain from our portable stimulator. The second method of control, also described in the 1 January 1965 report, involves rewarding electrical stimulation only. This system employs a single electrode, the tipa of which are located in revarding brain areas such as shown in Fig O. and relatively lower intensities of stimulation. The intensities required are vithin the output capebilities of our stinulator. A comparison of the two methods was presented in our report of 1 January 1965.

We have not exolored further tbe elicited control method: we have concentrated our field research efforts on the rewerd method. The results have been entirely satisfactory. Our 1 January l965 report described field control with three dogs: the fourth dog vas undergoing preliminery' training. Since then, that fourth dog in addition to a fifth and a sixth have been trained to track in a free field under the control of remotely triggered, rewarding electricel stimulation of the brain. In addition. - several parametric atudies have been undertaken vith those dogs in order to explore the control procese. A striking

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result of our vork heo been the relative ease with vhich a dog may be truined to respond in the open field. The several steps in the prccedure are as folloss:

a) Following implantation under Nembutal anesthesia, the dog is provided vith post-operative care in order to insure recovery.

b) Arter recovery, the electrode placement is tested for the result of stimulation. We have dispensed vith teating in a dog box (using a lever press as the behavior) and ve presently test by observing the free behavior of the dog in the small, fenced enclosure. The direct line arrangement employing a stimulator in the laboratory and the overbead connector is employed in these tests.

The effects of stimulation are assessed by observing the movenents of the dog when stimulated. With the appropriate electrode placenent, there is a clear tendency for the animal to repeat any movenent which is immediately folloved by stimulation-- the vell known reinforcement or revard effect. Thus, ir the dog is movirg forvard and that behavior is accompanied by stimulation, the dog vill continue to move forvard. A second important feature of stinulation is the strong tendency to initiete locomotion in the direction in which the dog's head ia\_oricnted. In fact, this latter feeture ie the key to the procedure. Thus, if the dog's head is

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turned to the left vith respect to the rest of his body. the dog vill begin moving to the lert upon the commencenent of stimulation. This tcniency permits directional control over the dog's position in the field. The two tendencies mentioned, rewerd and locomotion, are maximized by varying the intensity of the 100 cps sine-wave stimulation. The intensity vhlch, in the Judgement of the experimenter, provides the best results is chosen for a given dog. c) Following the above determinations, the dog, equirped with the portable stimulator, is shirted to the open field situation. This phase of the trrining technique is difficult to describe in vords-- its aim is to obtain precise, directionally controlled movement (i.e., tracking) in the field, Because of the necessity of adjusting the details of the procedure to esch individual dog, the overall technique may be poorly suseptible to coopiete autometion. Given that a particular dog is appropriately implanted, and the intensity of stimulation bas been found vhich maximizes forvard loccmotion and the reward efrect, the precise relationship betueen the dog's fine behavior and the delivery of stimulation becomes critical.

With Judicious application of stimulation by the experinenter, movement in a particular direction can be initiated when' the dog's heod is oricnted in thot dircction. Once the movenent is initiated, it can be maintained by intermittent stimulation vhich serves to

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reinforce moving in that direction. If the experinenter wishes to change the direction of movement at a particular point in the field, stimuletion is vithheld when the dog reeches that point. Very early in training, the dog learna that stimulation will be continued only ir be orients 1n a new direction. Thus, vhen stimulation is terminated by the experimenter, tbe dog moves in sball circles. When the dog's head is pointed in the appropriate direction, stimulation is again delivered and movement in the nev direction is initiated.

A similar procedure is folloved if the dog veers from the desired direction. The experimenter discontinues stimulation; the animal begins circling until stimulation is again delivered. He then moves forvard in the direction in which he was oriented at the time stimulation recommenced, and intermittent stimuletion is continued until the dog veers from the correct direction or until the experimenter wishes to change the direction of locomotion.

The individuality of each dog is expressed in the answers to such questions as:

1."Bhouid each stimulation delivered to the dog be of fixed duration, or does veriable duration provide better results?

1i. Are rapid burste of stimuletion better in that locomotion is therety racilitated, or vill rapid stimulation produce locomotion end then recoilt

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111. Whet are the particular bchavioral signa vhich indicate that control is being lost, and hov is control restablished?

iv. What kinds of behaviors are more easily controlled with a particular dog? For eximple, will he traverse a vater puddle, tall grass, etc., or should those gedgraphies be.circumvented?

We have found that the several dogs We have vorked with are idiosyncratic vith respect to each of the questions that must be answered. Once ansvers are obtained, bovever. field control becomes a relatively easy matter. It vould be difficult to overenohasize the importance of a behaviorally sophisticated end comvetent person handling the dor during the early training and even during the final performance of controlled field behavior. General principles defining such sophisticatior: cannot be given- among research people, the phrase "feel for behavior" sumzarizes the requirement. who bes ben with the principle investigator since the start of thc vork, bas capably identlfied a number of the problems involved in the developrent of the procedure acd bas solved many of them himself,

While the above considerations strongly suggest thet an eutomated procedure for trairing dogs to track in the open field is not promising, it must be emphasized that

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we have not explored the possibility at àll-- our vork has been concerned with the development of some procedure for obtaining remote control and an evaluation of its feasibility. It is conceivable, and even likely, that a common denominator across dogs cen be established and a procedure developed vhich vill provide for the automated training of the Bcout dogs.

d)' When the experimenter is feniliar with the 1diosyncrasies or a particuler dog, about one veek's vork, an bour to two hours per day, is sufficient to train the. dog to treck in the open field.

Two types of practice arrangements have been employed in our work:

i. General, open field patterns, with the precise pattern to be run predeternined by the experimenter. ii. Patterns defined by a matrix of 15 stekes in the ground, 3 x 5, each stake spaced 24 feet from another. This arrangement permitted running standard patterns for purposes of collecting quantitetive data.

k. Figure I shous the stimulation equipment we employ in our fie\_d work. The units are those menufactured Figure lA shous the transmitter. The unit.pcasures about 12 x 6 x b inches and 1s easily portable. The model shoun, bovever, does need e pover outlet; cozplete portability could be achieved by incorporating a battery

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The transmitter (Fig lA) and receiver-stimulator units (Figs lB and 1C). The latter are shown in place on the backs of experimental doge.

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A

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pover supply. Figures 1B and 1C show the rccciver-stimulator strapped to the backs or two dogs. The unit measures about 7 x 3 1/2 x 1 inches and veighe, including leads, connectors and small antennae, about one pound. Although some minor problems have arisen from time to tine in the use of the transmitter and receiver-stimulator system, its performance hes been, on the vhole, quite satisfactory.

5. Figures 2 to 5 show the results of the field control procedure. Each of those figures consists of several plates vith several 35 m. photographs per plate. The first photograph in each of those rigures shows the open field pattern through vhich the dog is to be guided. Alongside that photograph, snd each or the others in the figure, the saze pattera is reproduced. The arrovs on the pattera indicate the direction of movement of the dog through the pattera. In addition, note that a round marker appears alongside the pattern edjacent to each photograph, except the first, in the figure. The dot indicates the general position of the dog et the time that photogreph in the serics was teken, For purposes of eimpllfying locstion of the dog, a bleck marker ves affixed to each photogreph. The dog is ahown immedietely below the marker. By following the progression of dots alongside the patterns adjacent to the photographs and releting that progression to the poeitions of the dog in the sequence of pbotographs, an appreciation of the action may be geined. The three figures, 2 through 5, shov severel pattcrne.. Two dogs

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Figure 2

A sequence of photographs showing the coptrol of open field behevior vith a dog.

(See text for explanation of the several markers in each photograp.)

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Figure 3

A sequence of photographs showing a second field pattern being run by en experimental doe.

(See text for explanetion of the several markers in esch photogreph.)

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Still another pattern.

(See text for explanation of the several markers in each photograph.)

Figure 4

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Fig 4-4

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Fig 4-6

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A fourth pattern.

(See text for explonation of the several markers in each photograph.)

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vere enployed in running the several sequenccs. The patterns vere arbitrarily chosen, but deliberately kept pimple in order to facilitate presentation in the prcsent forzet. Unphotocraphed sequences were more complicated; the degree of behavioral control vas much as shown in the simpler sequences. It is clear from the data pres -nted that the experimenter bes excellent control over the bebavior of the unrestricted dogs.

6. Exemination of Figs 2 through 5 shovs an effect that vas found to occur in all of our dogs vhile being guided through a field pattern under the control of revarding brain stimulation. That effect is seen post clearly in several of the photographs where the dog vas close to the camera- Bee, for example, the middle photograph in Fig 2-2, tbe bottom two photographs in Fis 3-1, the middle photosreph in Fig 4-1, and the bottom photogreph in Fig h-5. In each cese, and for both dogs, the animal sniffs along the ground while folloing the psth selected by the experimenter- it seems as though the animel is following the path of an olfactory cue. It is entirely possible, bowever speculative, that that is precisely wbat is béppening, with the stimulation producing a central process like that produced by an olfactory stimulus which serves as a revard and evokes "folloving" or tracking behavior. While ve cannot confirm or infirm that interpretation of the behavior, ve can aek the question whether or not a dog can be trained to track a pattern with

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his head held high.

In order to examine thc possibility, another dog ves implanted and trained to track according to the proccdures described above. In this instance, hovever, rewarding brain stimulation vas delivered so as not only to initiste and maintain locomotion but also differentially in order to reisforce (the revard effect of brain eticulation) head position. The dog was given about two veeks of such training and his tracking performence in the open field vas fouod to be much like trat shown for the other dogs in Figs 2 through 5. This dog, bcvever, progressed through a pattern vith a distinctly different bead position. Figure 6 consists of three photographs taken during a tracking session. Note the position of the dog's bead in the upper two photographs- in both, the head points straight forvard rather than down at the ground. The center photograph gives only a suggestion of the exeggerated high head position that vas seen on occasio with this dog. The bottom photograph shows a reversion to a partial bead-down position. Wbile the lovered head occurred, it did so relatively infrequently, and the bigh head postiion could be quickly reestablisbed by monentarily vithholding revarding etimulation. It may be concluded, therefore, that the bead dowm, sniffing behsvior is not a necessary concoaitant oi open field behevior control vith rewarding electricai stimulation of the brain. We cannot state, however, that it is irrelevant-- the present experinent may have involved the

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Figure 6

Photographs showing the results of an experiment in vhich a dog was trained to traverse  controlled pattern with bead held high.

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suppression of an irportant though not necessary concomitant. 7. The above vork, which exanined bchavioral control through arbitrery petterns in the open ficld, vas not casily susceptible to quantirication. In order to obtain quantitative data vith respect to Bome of the elementary parameters of stimulation, such as the durstion and intensity of each train of stimulation delivered to the dog during the course of  pattern, a matrix of stakes was placed in the ficld. The patrix consisted of five rows of three stekes in each rov. Twentyfour feet separated adjacent stakes in the rovs and columrs. A stenderd pattern and its mirror image could be run fron day to day and quantitative deta in terms of elapsed time from stake to stake could be taken. Elapsed time was studied as a function of train duration and intensity of stisulatione, Within a renge of intensities and durations producing no behavioral control at the low end and clearly disrupted performance at the high end, relatively swall differences in time measures vere obtained as a Nunction of intensity and duration. A general conclusion stemming from these experiments is: intensities and durations markedly lover than the optimum produced increases in the times taken to traverse a pattern. These time scores, however, were frequently meeningless in the sense that control over the dog's behavior had besn loat and the performance completely disrupted. Intensities and durations vithin the optimum range produced stable perfcrmance measures from day to day. The shorter

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durations (nbout 200 mscc) nnd modcrate to high intensities vithin the rcnre arc preferrcd: the data showed sligbtly faster running tioes at thosc intensities and durations. Increnses in intensity and duration beyond optimum values produced longer running times due to a variety or effects, including recoil..

Although the behavior sequences sbows in Pigs 2 through 5 did not employ the stake patterns just described, the stakes may be seen in the photographs.

8. Oue of the interesting questions regarding the coptrol of field behavior in dogs by means of brain stimulation reward concerns the effects of competing reinforcers. The question 'we entertained in arecent experiment vas: if a dog is under the control of brain stimulation reward end is running a coatrolled pettern in the field, bov likely is it that be vill leave the pattern when given the opportunity to obtain a different reinforcer?

Two implanted dogs vere deprived of food and slowly reduced to Bo% of their free feeding veights. They vere tben megazice trained, 1.e., a lerge metal box with feeder atteched ves located in the field (see Fie 7). Through control circuitry located in the laboratory and a svitch in the band or the experimenter, the dogs were trained to run into the box at the sound of a tone (the Bpeakers can be seen in the center photograph of Fig 7-2) in order to obtain food. No brain stimulation wes delivered during these training sessions, and

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Figure 7

Response to the tone in an experiment designed to investigate competition between food reward and brain stimulation, vith the latter serving to control free-field bebavior.

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care vas teken never to present the tone (and, bence, revard the immedietely preceeding behavior) so that the dog learned"- to "squat" near the box. "Rather, the dogs learned to roam C.
the field freely and to ruu to the box only and vhen ever the tone sounded.

When the food maintained behavior vas under gocd stimulus control, i.e., rapid approach to the box at the sound of the tone, sessiors were run in which no tone presentations were used. The dcgs vere trained to run a rectangular pattern for brain stiñulation during these sessions. The food box vas located immediately outside the rectangle, at the center of a long side. The dimensions of the rectangle vere 48 x 24 feet. Note that these dimensions consist of six 24-foot legs as defined by the ground stekes described earlier, vith one leg at each end of the rectangle and two legs comprising each side. When the performance for stizulation vas stable. competition sessions vere run as fcllows:

Two experimenters vorked together; one guided the dog through the rectangular pattern emplcying brain stimulation, while the other operated the tone-feeder control. The points in the pattern at which the probes occurred were deterwined by the second experimenter and vere unknown to the first-- a blind procedure.

a) Ueing this techoique, probes vere appiied, 1.e., the tone turned.on, during one leg ot the pattern and during a.. differeni leg for each eircuit of the rectanglc. On anotber

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day, the probe tones were kept on for two consecutive legs of the pattern.

b) The above proccedure ves repeated, but the intensity of stimulation used to control the behavior of the dogs vas veried from optimum (2500 microemperes for one dog and g00 microamperes for the other) to several values belcw optimum.

The results obtained on the competition tests were strikingly orderly and alloved general conclusions which epplied to the two dogs. First, hovever, note the experimental arrangement in Fig 7. The photographs vere taken at the terminetion of training to enter the box for food, i.e., before the brain stimulation sessions vere run. Te food box can be seen in each of the photographs A through F. Photographs A through E show a single sequence. In photograph A, the dog (note the dark marker indicating the position of the dog) is facing away rrom the food box, and that photograph vas taken before the tone vas turned on. The tone bad just been turned on vhen photogreph B was taken; the dog is on bis vay to the box. In photograph D he is entering the box, and is leaving it, having consumed the food, in photogreph E. Photograph P sbows the second dog entering the tox during a tone trial.

The general conclusions resulting from this experiment vere: a) At optimum levels of stimuletion intensity, where excellent control of the field behavior vas obtained, peither dog entered the food box even once when the tone

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vas presented for either one or tuo lecs of the pattern. The control exercised by brain stimulation was sufficient to compete successfully vith a food reinforcer l00% of the time.

b) At the lowest intensities employed,"2000 microemperes and hoo microamperes for the tvo dogs, control by stimulation vas virtually nonexistent. Both dogs entered the food box on l00% of the tone presentations. At the lovest intensities, therefore, food provided maximum coopetition. e) At"intermediate intensities of stimuletion, clearly intermediate effecte vere obtained. Whether or not the food competed successfully depended on several other factors.

i. If the dog vas fecing the rood box when the\_tone came on, he vas more likely to enter then if he vas fecing avay from the food box.

ii. If the dog had imediately before been run under higher intensities of stimuletion, be vas less likely to erter the food box than if the same intercediate intensity was tested following a lover intensity test.

ili. The derree to which each of the reinforcers ccntrolled the behavior with intercediate intensities of stimulation dependcd on the level of the intetediate intensity. Food control vas veaker at higher intermediate intensities and stronger at lover interqediate Intensities.

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In ,swwmary, then, brain stimulation emerged as a powerful peans of bchavioral control. Under optinua conditions, a strong reinforcer like food could not compete. Uader less than optimum conditions, food was able to compete to s dcgree inversely related to the inteneity of etimulation used to control the dog's behevior.

B. Summary and conclusions

The results of our vork on dogs involving the control of open field behavior employing remotely triggered electrical stisulation of the brain have demonstrated the feasibility of such control techniques. Control of the behavior is positive end can be maintained over relatively long periods of time. Training a dog to perfors in the open field under the control of rewarding electrical stimulation of.the brein cen be accomplished ia a short period or tine-- about 15 bours of work per dos is a fairly typical value.. Advantages of the system we developed are:

. 1. Behavioral control is obtained et intensities of stizulation wbich permit portable stimulators of moderate size and veight. Highly specialized minieturizetion is not necessary. although such techniçues might reduce even furtber tbe size and weight of the unit.

2. The use of a single electrode provides for a relatively simple surgical preparation.

3. The syetem is "quiet," 1.e., environmental stimuli such as tones and clickers are unnecessary. Stimulus control over the behavior is exercised by the brain stimulation which Berves

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aleo to revnrd precise movenents and initiate locomotion. 4. It has not been necessnry to epploy aversive elcctrode placements, 1.e., placements at which stinulotion is punishing. Disadvuntages of the system as developed are:

1. While the electrode preparation hns been satisfoctory for research purposes, it is unlikely that it would serve over very long periods of time. Better anchoring and surgical procedures vould be necessnry.

2. The system is restricted to line of sight. It is necessary for the experimenter to observe closely the orientation of the animal and, purticularly, bis fine movements. While opticnl systems could extend the range of such observations, visual obstncles such ns trees, hills, folinge, etc.,ccnnot be surmounted. Electronic devices providing out of sight monitoring might extend the range of the system.

3. Individuality among dogs is such ns to susgest thct automated training procedures mieht not be a simple motter to develop, but it is vorth an attempt.

C. Bupporting resenrch

Resenrch which supported our primnry aims wes perforzed during all phases of the program. Initially, and particularly during the time before completion of the nev resenrch loboratory, ve concentrated our activities on research at the level of the rat. With increasing sophiatication, and the solutioos to problems such as electrode placement in the dog and the development of the: portable

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receiver-atimulator unit, increasingly more ettention was focused 'on dog research. The Bignificant resulte of the letter efforts were surmarized above; this section of the report surzarizes the research subsidiary to the dog work. Since much of the surporting research has been sumarized in previous reports from this laboratory, our description of the experincnte vill be relatively concise.

The experiments to be reported belou involved the use of Beveral schedules of reinforcement. A schedule of reinforcement may be defined as a rule vbich relates in an explicit manoer the occurrence of a reinforcer and the behavior of an organiso. In laboratory prpctice, these rules are interpreted into relay logic, and electricel circuits consisting of relays, stepping switcbes, tiners, etc. are constructed. While knovledge of the electrical circuit enployed in each experiment 1s unnecessary, a statenest of tbe behevior-reinforcement rule, or schedule, is necessary. Each schedule that we employed 1s identified in the appropriate place. In soue instances. "reminder" definitions have been included. For purposes of completeness, hovever, a list of the reinforcement schedules ve employed vill now be presented, and reference to this list may, depending on the reoder's background, aid in reeding what is to follov.

Response or behavior: An overt, observable movenent of the organism. An ingtrumental respoose.is B skeletal muscle movezent thst serves to change the organism's eovironment in soze identi-

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fiable way. In the laborotory, a switch operation by peans or a lever press (rat) or a key peck (pigeon) have been most orten used.

Reinforcenent: An instrumental reinforcer is a stimulus change vhich increases the probebility or frequency of'a behavior which closely precedes it. The occurrence of such a stimulus change is a reinforcement. A positive reinforcer is synonymous with the colloquial "revard." There is no colloquial equivalent for s negative reinforcer, but the latter are stimulus changes which punish, generete escape, and motivate avoidance.

Schedule of Reinforcement: A rule relating tbe occurrence of reinforcing stimulus changes to behavior.

Ratio Schedule: A schedule of reinforcczent in vhicb the occurrence of a reinforcer is made dependent on the occurrence of a number or count of responses.

1. Fixed ratio: the reinforcer is dependent on the occurrence of N responses. and the size of N does not change froz reinforcement to reinforcement.

2. Continuous reinforcement: A fixed ratio schcdule in vhich N equals one response. Tbus, each occurrence of the criterion respoase is reinforced. All other schedules are intetittent reinforcement schedules.

3. Progressive ratio: A ratio schedule in which the size of N iocreases (in a syetenatic fashion) throughout an experinental seasion. The eize of the initial N, the progressiou constant

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(1.e., the increment to N) and the nwber of reinforcements peritted at each value of N, define the schedule. In the experiment reported below vhich crployed a progressive ratio: Initial N-- on? response.

Progression constant-- three responses.

Number of reinforcements-- five at each veiue of N.

Interval Schedule: A achedule of reinforcement in which the assignment or the availability of a reinforcenent depends on the time elapsed since the preceding reinforcement. Note, bowever, that a response is required to deliver the reinforcenent once assigned by the achedule,

l. Fixed interval: The elspsed time for the assignnent of reinforcements is constant from reinforcement to reinforcement.

2. Variable interval: The elapsed time varies from reinforcement to reinforcement in an unsystematic fashion. The schedule is Identified by the mean (arithnetic) of all the intervals programmed. The distribution of intervals should also be specified; arithmetic distributions vere employed below. and the largest interval in' the program vas alvays tuice the mean of all the intervals. The shortest interval was always several Beconds.

Differential Reinforcement of Lov Rate (DRL): A Bchedule designed to generate a "low" rate of responding. A minimum interval of time must elapse (the DRL interval) betveen successive responses

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for a response to be reinforced. "Eerly" responses start the interval anev, and in each instance of an early responsc, the accunulated elapsed time is lost.

Extinction: After a behavior has been reinrorced according to a schedule, withdrawal of the opportunity for reinforcement of the criterion behavior defines extinction.

Chain Schedule: A compound schedule in vhich more than ope requirement must be met in succession for a reinforcement to occur. A subsequent requirement is not initiated until the prior requirement has been satisfied. The situetion is arranged so that a distinct environbental condition (stimulus) is associated with each requirement in the sequence. The occurrence of reinforcecent reinstates the initial requirement.

Multiple Schedule: A compound schedule in vhich more than one simple schedule is prograrmed, each leadin? to reinforcerent, and eacb component is correlated with a distinct environmental conditioo (stinulus). Several instences of each sinpler schedule may occur in succession; the siopler schedules may change systematically or unsystematically with regard to sequence.

Concurrent Schedule: A cospound achedule in vhich tuo or more simpler schedules are in effect simultaneously. Where a different response is requlred for each schedule, as on differeat levers, the anizal may change freely among the several ochedules. Reinforcements are assigned by each schedule according to the rules defining each schedule.

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1. An enrly experimcnt studied the performances of three rats on fixed ratio schedules of reinforcement. On some days, the behevior was revarded with brain stimuletion delivered to the posterior hypothalamus and on other days in the conventional fashion vith food pellets. Only one type of reward vas used on a gives day. Our results demonstrated (in all three rats) t.at perforoance vith brain stimulation as the reinforcer vas clearly inferior to performances maintained by food pellets. In general, pauses in responding after reinforcement, a typical feature of fixed ratio performance, vere considerably lengthened vith brain-stimulation. revard. Increases in the intensity end the duration of the train of stimulation served to temporarily "inprove" performance. In a chronic extinciton test in which one hour of extinction was preceded by 20 reinforcements on fixed retio 10, more responses vere emitted when the 20 reinforcements of the daily test session vere food pellets as compered vith a session in vhich the 20 reinforcemente vere brain stimulation.

2. Our attention turned to devising a method for paintaining more behavior with brain stimulation reverd than we were able to maintain in the firat experinent described above. Tvo experinents vere performed, In both, a schedule of intermittent reinforcement vas programmed on one lever of a two-lever rat box. The consequence of responding on that lever wns the insertion into the box of another, retractable lever. Brain stimulation (posterior hypothalamus), one train per lever press, vas programmed on the Becond lever and a fixed number of stinulations (continuous

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reinforcement) vas permitted. Upon complction of that aumber of stimulations, the lever rctracted from the box and the rat could reproduce it only by vorkipg on the other, schedule lcver.

In the first experiment, a progressive ratio. vas progrezmed on the Sixed, echedule lever; in the second experiment, a variable interval schedule of 30 seconds. Both experiments gava evidence of better schedule performance, a'higher maximum ratio in the progressive ratio experiment and e higher response rate on the variable interval schedule of the second experiment, vith increase: in the number of stimulations permitted on the retracteble lever. 3. Based on the data Just reported, ve undertook a Eeneral and fairly extensive experiment 1n order to determine the Reneral characteristics of schedules of intermittent reinforcenent employing the two-lever, multiple-stimulation procedure described above. Septal and posterior hypothalamic placements vere used. Specifically, we vere intcrested in determining whether or not ve couid maintain schedule performances in the same range of parameter values as ordinarily used with food as a reinforcer. The reinforcer in these experiments, hovever, was 20 to 100 stimulatioa-reinforced presses on the retracteble lever. The scbedules studied were programed on the fixed, nonretractable lever and were: fixed ratio, fixed interval, variable interval, differential reinforcement of low ratee.. In all cases, the performances on the fixed lever approximated those typically obtaines vith intermittent sbedules of food reinforcenent. Transitions fron one schedule to another vere also typical. An

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implication 'of this vork was: it should be possible to maintain complex performances with our dogs in the field. The critical variable in Genereting performances using brain-stimulation reinforcement wes not thc nature of brain stimulation as s reinforcer, but rather the precise vey in vhich it is used. Specifically, the present experiment demonstreted that if a brain-stioulation reinforcement is defined as several re: onse-produced traing of stimuletion rather than s sinele train as is typically the case, substantial behavioral output and characteristic schedule performarces could be obtained.' Septal placenents, bowever, vere inferior to bypothalanic.

b. The proceáures just described may be classified as chain schedules of reinforcement, 1.e., one performance bas as its conscquence the opportunity to engage in another perforcence which leads to reinforcement. Employing a veriable interval schedule on the fixed lever (initial member of tbe chain) and manipulating the parameters of trein-stimulation revard on the retractable lever (terminal member of the chain) a series of experinente vas urdertaken to systematically study the efrects of stiouletion parameters. Posterior hypothalasic placenents were used throughout, except in the second experiment (Duration) in which septal placements were also used.

a) Intensity: Pive stimulations vere permitted in the terminal chain member. The intensity, measured in microanperes, vas the same for'each of the five stimulations. That intensity vas changed gystematically, hovever, in order to study the

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relationship between tuo rcsponse ratcs: the rate at vhich the rat pressed the lever on the variable interval schcdule in order to gain access to the stimulation lever and the rate at which the sitmulation lever vas pressed to produce stimulation once it vas obtained. Our results indicated that the variable interval rate of reaponse was low at low intersities of stinulation, increased viti. increases in the intensity of stimulation and increased still further at the bighest intensities of stimulation. The rate at vhich the rats accepted stimulation vas lover at the extremes of the intensity variable, ise., maximum rates of self-stimulation occurred at moderate intensities. These results vere interpreted to mean that the rate of self-stimulation in the terminal meater of the chain vas a: poor predictor of the behevior-maintaiping property of brain stimulatios.

b) Duration: A similar procedure vas employed vitb e single train of stimulation permitted on the retractable lever (terminal chain member). Again, a variable interval schedule of 30 seconds on the permianent lever (initial chain member) assigned opportunities to respond on the stimulation lever. Train duretions from l25 msec to 15 sec vere studied, and the primery datuz vas the rate of responding on the varieble interval lever. The results vere not clear: they suegested that the "best" performances, 1.e., highest variable interval responee rates, vére obtained at train durations of about five seconds. Somewhst lover variable Interval response ates

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occurred.at the longest durations studied. We could not. however, unambiguously attribute the lower rates to the longer train durations-- it vas possible that the lover response rates at the longer train durations represented drifts in the baseline rather than 'effects of the experimental variable. Our experiance with this experiment motivated us to seek new methods of studying brain-stimulation variables; the use of concurrent scheduling procedures, to-be mentioned later, vas the result.

e) Frequency: The frequency of a sine vave is known to affect the performance of rats in a brain stimulation experiment in which the behavlor is continuously reinforced, 1.e., where each lever press produces stimulation. We examined the effects of sine-vave frequency (peak-to-peak current intensity and train duration held constent) within the context of the chaining procedure outlined above. In this case, the variable interval 30 sec schedule led to a fixed number (2o) of stimulation-reinforced lever presses on the retractable lever; the variable interval response rate was evaluated at each of several different frequencies of the stimulation sire wave from 20 cps to 2500 cps. The results vere clear: bigh response rates on the variable interval scheule were obtained with sine wave frequencies betveen l00 cps and 500 cps. The peak of the runction relating rate and frequency vas approximately 100 cps to 200 cps. On the basis of these date, the portable stimuletor ve

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employed in our dog vork was built to provide a l00 cps sine weve.

Subsequent to that initial study, a more complex study was performed in which train duration, current intensity and sine-wave frequency were manipulated in a statistical, factorial-type design. In this experiment, a single stimulation-reinforced press vas permitted in the terminal chain member, i.e., on the retractable lever. The above findings vere confirmed with the additional result that efforts to manipulate train duretion and current intensity so as to keel peak-to-peak ricrocoulombs constant did not produce equal rates of responding on the variable interval lever. The coulcnb, or microcoulomb, may not be a useful indicator of reinforcement value,'as has been suspected.

5. Employine the more traditional self-stimulation technique,

i.e.,  single lever on which Belf-stimulation mey be programmed for each press or according to a schedule of intermittent reinforcement, jin our laboratory performed an experinent in which train duration and current intensity vere Jointly varied. The performance measure was response rate on a scbedule of continuous reinforcement, i.e., stimulation delivered for each press, and on a fixed ratio of five to one. Both septal end median forebrain bundle placements were studied in the saze animals. Repsonse rates for septal stimulation were consistently lover than for median forebzain bundle stimulation. A train duration of O.l sec vas consistently "best" for septal stizu-:

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lation, but the train duration producing maximum response rate for median forebrein bundle stirulation depended on current intensity. Higher current intensities, 400uA and 600uA produccd increases in response rate with increesing train.durations up to about 0.2 to 0.3 sec. Response rate decreased beyond that point. Optimum train durations vere longer for the fixed ratio Bchedule. The results were interpreted as indicating that microcoulombs is al important determinant of self-stimulation rate. That conclusion differs from the conclusion of the experiment mentioned above in which sine-wave frequency, train duration, and current intensity vere jointly varied in the two-lever procedure. The question regarding the possibility of relating reward value of brain stiπulation to a single electrical dimension is not answered, and it remains as an interesting possibility. 6. Another experiment by Dr. Investigated resistance to extinction as a function of the method of reward presentation. Brain stimulation revard (median forebrain bundie) vas presedted for one group of animals immediately es the lever was depressed in the traditional fashion. For another group of animals, lever dopression activatcd a dry water dipper in another part of the box, and licking the dipper produced brain stimulation (a chain schedule). Suitable controls vere employed, including a standard vater reinforcement group. Extinction scores, where lever pressing no longer led to brain etimulation in the first two groups or water in the vater control group, showed maximu resistance to extinction 1n the veter control group. Significently, resistance to extinction

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was greater in the brain stimulation group which obtaiccd stizulatiop by licking the vater cup as compared with the group that received stimulation in the treditiooal frshion, i.e., "on the lever." These results to Bome extent illuminate our findings reported above (paragraph 3 of this section) in which substential intcrmittent schedule perrormances were paintained through the. use of & chaining procedure in vhich the terminal member of the chain consisted of access to a lever on vhich a predetofnoa z=ber o etipulations vas programed on continuous reinforcement. Evidcatly. the multiple stipulation feature of that vork vas only one of the variables respousible fcr the result-- the chaining technique vas alsoimportent. A general conclusion seems to be thet as the methods employed to study revarding electrical stimulation of the brain approach more and more closely the methods employing conventiopal reinforcers, differences betveen brain-stimulation revard and the conventional revards tend to vanish.

7. Because ve ente-tained the possibility of having to employ en aversive electrode placement in the dog in order to obtain control over the free-field bebavior, ve studied the effects of eversive stimulation contingent upon a lever press, i.e., punishment. Rats, vith electrodes implanted in the medial lemrksgs and lsteral geniculate areas, vere reduced to 80% of free feeding veight and then trained on a variable interval one minute achedule to press a lever for food pellets. When the variable interval performance vas stable, stimulation vas introduced for each lever presa. Response rate vas studied as

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as a function of the intensity of stimulation. Typical punishment effects vere found: the rate on the variable interval schedule varied inversely with the intensity of stimulation. Stated othervise, the more intense the punishing stimulus, the lover the frequency of the behavior vhich produced it. That responding ves meintained at ell vas due, of course, to the food pellets vhich served as a source of positive motivation for the behavior. Further, when stimulation ves discontinued, recovery occurred, 1.e., the response rate returned to the previously unpunished level. At the very higbest intensities of aversive stizulation, recovery was delayed in that the lov response rate persisted for some time (minutes) arter the removel of the aversive contingency. After low intensities of stimuletion, recovery vas almost immediate. Significantly', compensation, or a tendency to "overshcot" the prepunishment baseline rate, vas seen after moderate intensities of punishment. All of the results of this experiment conrormed to rindings reported in the literature employing conveotional aversive stimuli, such as foot shock in rats.

8. An exferiment vhich provided crucial data in designing the free-field control system for the dogs was performed insiãe the laborstory and employed rats as the experimental subjects. The procedures and results vere described in detail in our report of 1 January 196s. In summary, a smell, vcoden "field" vas prepared. It measured approximately 8 x 4 feet and vas located in a corner of the laboratory. 'A rat, vith electrodes located in the region of the mamillary bodies of the posterior hypothalamus, could

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roa freely over the field and vas connected to a atimulator by means of a flexible cord hung from a pulley device over the center of the field. The experimenter vieved the rat by means of a mirror inclined L5° from the horizontal, Several procedures vere attempted in order to control the field behavior of the rat. It vas discovered, almost by accident, that if sbort trains of stiaulation ere delivered to the rat at a fairly rapid frequency, forvard locomotion in the direction of hend orientation vas initieted. The intensity of stimulation vas criticel and bad to be determined empirically for each rat. Too low en intensity. and locomotion vas not initiated; too high, and recoil vas obtained. The procedure, then, for moving the rat from a point in the field to another point vas to turn on stimulaticn when the rat's bead vas pointing in the desired direction-- stimuletion vas kept on (200 msec bursts, three per second) as long as the rat loconoted in the desired direction. The rat quickly learned to vave its bead from side to side when stimulation vas terminated, because that behavior was revarded with the rerewa) of stinulation. If a change in direction wes desired, or if the rat veered off course, stimulation vas terninated. The rat remained stationary in the absence of stimulation and "sought" the nev direction by means of-the aforementioned hcad movement. In a sbort period of time, eood control over the rats' free-field behavior was established.

We next exanined'the control procedure Just deßcribed under more stringent conditions from the point of view of maintaining behavioral control. Obstacles vere placed in the field vhieh

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the rat had to surmount in order to continue locorotion in a direction which maintained stimulation. The obstacles were easily surmounted, and little ir any degradation in performance vas observed. Finally, the field vas flooded, 'and the rat ves required to leave a corner platform and swim in order to receive stimulation. Acain, control over the direction of locomotion was positive. The significance of the finding vith regard to awimming rests in the pature of the behavior-- it is not "rat like." Apparently the control technique is powerful enough to generate and maintain control over a bebavior which is pot common to the apecies. While svimming has been studied in rats over the years, ve vere nevertheless impressed vith the finding.

Because the effects just described vere obtained in three out of three rats, it seemed promising as a technique for the dog. It will be recognized that the procedure bas such in common with the dog coutrol procedure described earlier in this report.

D. Additional regecrch

This clessification of research activitics is included to cover research vhich vas aimed at exploring the properties of brain stimulation as a reinforcer, the development of tecbniques to accomplish that goal, and an exploration of some izplications of our findings 'from other experiments.

1. In the typićal brain stimulation experinent, stimulation occurs imediately upon closure of the lever switch-- the only

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delays involved are those that result from the use of electrical prosramming devices, and such delays are calculated in milliseconds, Food reinforcement involves delays betucen a lever press and the receipt of food reinforcenent in the order of s second or so. Employing a multiple schedule technique in which the rat had to alternate between two levers to obtain successive reinforcements (perseverative respcrses going unreinforced) ve correlated ope stizulus in the multiple achedule vith a zero delay betveen the lever press and stizulation and the other stimulus vith a half-second delay. Posterior hypothalamic electrode placenents vere used. The two deley conditions of the πultiple scbedule alternated every five minutes. The purpose of the experiment vas to study resistance. to extinction as a function of the zero and half-second delaysi the nadn data turred out to bc the performance of the rats during the half-second delay condition. With po delay, the alternation between levers vas smooth; with a balf-second delay, rather bizzare response topographies developed betveen a lever press and the occurrence of stimulation-- the rat vould stand erect on its hind pavs, forepavs extended and head cocked in an unusual positioo. That both the emooth and the bizzare topogrspkies occurred in the seme rat suggested that the latter vas a conditioned response rather than an elicited motor effect of the stimulation. We speculated vitb regard to the genesis of the delay behavior and suggested that it could have resulted

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from the instrwental shoping of an originally classically conditioned motor response. To investigate the possibility 'of classical conditionine, two new rats were employcd in e classical conditioning experinent. A brief tone vas folloved a half-second later by brain stinulation. No instrumental response vas required to produce the stiaulation. of course, and the intensity of the stimulation was set at a level that produced an easily observable bead cock, We succeeded in conditioning and then extinguishing the bead cock. Our dats vere interpreted as being relevant to the discriminative stimulus hypothesis, and ve suggested that the logical conclusioo that brain stimulation does not require a consummatory response cannot be used as evidence against the discriminative stimulus hypothesis, which relates the discriminative and reinforcing properties of a stimulus. A half-second celay betveen a stimulus and reinforcinf brain stisulation offers emple opportunity for responses ether than consummatory to come under the control of an environcental stiqulus.

2. A theory of brain stimulation in the current litereture identiries a dual role for each response-produced stioulatioait rewards the response in the conventional fasbion and also provides notivation for additional responding. Thus, the rat presses the lever because previous stioulation has rewarded the lever press and also motivated further lever pressing. This theory makes an unusual prediction vith regard to extinction

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after continuous reinforcemeut. It ctates that extinction is essentially independent of the number of unreinforced responses and primarily dependent on the time since extinction began: The prediction follovs from the theoretical postulation of a time-dependent decay process in the level of the motivation, i.e., vhen the atimulator is turaed off (extinctioa) the level of motivation decays to zero (presumably). At thet point, extinction is complete. The decay process is independept of unreinforced responding during the decay interval.

We examired some inplicetions of this theoretical prediction and obtained mixed evidence. Posterior hypothalamic electrode placesents vere used. After continuous reinforcement for léver pressing, the lever vas eutomatically removed fros the rat box for a period of 22 sec. When returned, the stioulator had been turned off, i.e., extinction vas introducei. The number of responses emitted vas approximately the same es in a condition vhere the lever was not removed from the box and extinction responses vere counted starting 22 sec after the stimulator was turped dff. The theory was confired- the number of extinction responses after 22 sec since the last stimulation vas independent of whether or not the lever ves present (and responses occurred) durine the 22 sec interval. As a further test of the theory, ve repeated the cordition dcscribed above in vhich the lever was removed fron the box for the first 22. sec of extinction. Nou.. however, "free" stimulations vere delivered to the rat at a rate of one stizu-

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latico per second, This operation should retard or prevent the decay of stimulation-induced motivation, and thc nuater of extinction responses occurring when the lever is returned to the box should be greater than when "free" stimulation is not given during the 22 sec interval. That result vas obtained. As a final test of the theoretical implications of the drivedecoy interpretation of brain-stimulation revard, we monipulated the conditions of training. i.e.. before extinction testing began, Wbile the rets vere being trained to press the lever for continuous relnforcement, the lever vas renoved fro the box every so often for 22 sec and then returped to the box for continued stimulation-reinforced respondine. After this type of trainiag, extinction tests with and without lever removel (as deacribed above) vere run. The neat relationships failed to appear. The theory. bowever, predicts that the same relationships should have obtoined,"since extiuction 1s postulated to be a function of drive decay and pot pethod of training. We concluded that the theory is of limited generality.

3. Because the cheining procedure used extensively in the research reported above vas susceptible to baseline drirt (see Section C, part. Lb above), ve became interested in devising a better method for studying the kinds of problezs in which we vere interested. The technique ve have explored and found to te markedly superior to the simple chaining procedure involves the use of concurrent ecbedules. With

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this procedure, tvo schedules of reinforcement aro progrerzed for the rat, one schedule on each lever of a two-lever box. Any schedules may be programmed, but, for theorctical and practical reasons, variable interval schcdules were used in our work. The programmed schedules run independently. Under these conditions, rats typically respond on both levers and generally obtain the reinforcements assigned to each of the tvo levers within a short period of time after assignzent. The critical feature of the procedure which makes it useful in the analysis of behavior is the fact that the proportion . of the total responses exitted on each lever is functiozally related to such variables as the relstive frequency of reinforcement on the two levers, the amount of revard per reinforcement on each lever, ete. Hence, the proportion of responses emitted on each lever in the concurrent schedule may be studied as a function or dirferent intensities of stimulation, different train duretions, different siue-vave frequencies, etc.,programmed concurrently. Since the ret. samples both experimental conditions in a short perioa of time, problens of baseline drift are attenuated. We po longer attempt a comparison betveen performances seperated by several weeks. We do pot mean to impiy that concurrent schediling procedures are the solution to all ills-- there are nev problems in the use of concurrent schedules, but ve have found such schedules tc-be superior to our earlier procedures. Soze experisents employing the procedure are nov described. Agais,

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posterior hypothalaric plocenents vere c=plojes.

a) Variable interval scrcdules of ore ein vere prcsrr=e! concurrently. The reinforcc=cnt on opc er the schesulcs vas a fixed, standard number of sticuletion rcinforccd lever presses delivered on continuous reinforccrent. The punher of stimulation-reinforced lever presses per reinforcement on the other lever was varied over values of 1, 2, 3, 5, 10, 50 and 100. The standard ageinst vbich each of those velues vas pitted on the first lever was one stimulation in one experiment and l00 stizulationg in another experiment.

In both experiments, the proportion of responses, i.e., relative rate of responding on the tuo levers, vas greater on the lever for.which variable interval respondirg vas reioforced by a larger number of stimulations. As the number of stimulations approached equality at either the one-one or the 100-l00 conditions, the percentege.of responses on each of the two levers approached 50%. The sbapes of the functional relations obteined paralleled previously published data cn concurrent schedules, On those grounds, we vere encouraged to atteopt further applicatione.

b) It is possible to deliver a fixed stipulation tice to a rat by varying the train duration per stimulation Jointly with the number of such stimulations permitted the rat. Thus, for example, five seconds of stimulation may be

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delivered in a single 5-sec train, in two 2.5 sec trains. ete. We examined the rats preference for train duratiors of 1.2, 2.4, 4.8, 9.6 sec, ench paired vith a number of 120 msec trains so chosen that total stimulation time ves the same. The sehcdules programned on the two levers vere variable interval one min schedules; the reinforcer for one of the schedules vas the single train of stimulation, and the reinforcer for the other schedule vas tke multiple stimulation condition. The date examined were the proportion of responses emitted on tbe two levers. The data vere unequivocal in pointing to aleck of preference for one method of stimulation as compared vith the other..

In order to deternine whether the concurrent performances vere sensitive to the experimental variable, so that the conclusion of equal performances implied no preference rather than no experimental control or an insensitive beeellne, yarlous degrees ef ineguelity vere introguced: A single train was favored by reducing the punber of l20 psec stimulstions paired with the single train, and the multiple etimulations vere favored by reducing the duration of the single train. Both types of manipuletions resulted in shifts in the proportions of responses emitted on the two levers in the expected directions avay froz equality. We concluded, therefore, that the equalities previously obtained represented "no preference." The electrode placements vere in the posterior hypothalarus.

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e) An'important feature of concurrent veriable interval schedules Is the change over deley (coD). If one of the schedules assigos a reinforcegent vhile the rat is responding ou the other scbedule, the first response after a change to the concurrent lever will ordinarily produco the assigned reinforcement. With a COD, however, the first response does pot produce the assigned reinforcement but rather Btarts the delay timer. The first repponse to occur after the deizy timer times out produces the assigned reinforcement. The d-lcy serves to "punish" and thereby reduce the frequency of change over responses, i.e., switches from one lever to the other. Employing the concurrent procedure with a short COD (a balf to several seconds) an interesting relationship bas been reported in the literature. Pigeoos distribute their responses on the two levers (or keys) in the same proportion as variable interval schedules assign reinforcements. In other vords, the relative rate of responding equals the relative rate of reinforcement. Thus, if, for example, the pigeon obtains one third of its reinforcerents on one of the keys, one third of the responses will be emitted on that key. As stated above, the reinforcement schedules employed in these experiments are variable interval schedules; these schedules permit a vide range of response rates vith little or po differencé in reinforcement frequency. An inplicatios of that property of varioble interval shcedules ia the fact

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that the motching relation stated above is not trivial; relative reinforcement rate could take on & single value vith videly divergent relative response rates. The fact that relative reinforcepent xate ratches relative response rate, in spite of the above considcrations, suggests that the relation may be theoretically icportant.

While it is known that the COD is important in producing the matching relation, its exact role has not been experimentally determined. Tvo possibilities exist: matcbing occurs provided a Cod of some size is programmed; alternatively, matching is an artiract of the tendency for a COp to "ampliry" a bias for one of the schedules, and the degree of amplificetion is a function of the size of tbe COD. The second interpretation states that matchirg will occur only with a criticelly chosen size of COD.

In order to examine the two possible interpretations of the role of the Cod in the matching relation, four rets vere implanted vith electrodes in the postericr bypotbalamus. Two were placed on concurrent varieble interval schedules of ue end a half minutes; te other two vere placed on a variable interval one minute schedule concurrent with a variable interval three min schedule. For all the rats, CoD was varied from tero to 20 secunds. In conformity with the second interpretation of the role of the COD, a'smooth and approximatcly linear, rising unction relating Cod to proportion of responses on the

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one minute variable interval echedui: vas obtaincd vith the rats on the concurrent one minut.-ihrce minute schedulcs. "Matching" occurrei when the functioi. passed through 75% at  COD cf about 10 sec. At a zcro sec COD, the function vas at apfroximately 50%; at e 20 sec cOD, it vas st approximately 90%. A function at 50% across all cods vas obtained with the rats on the concurrent one and a halr minute schedules. That result vas expected, since the equal variable interval schedules provided no bias on vhich the COD could operate.

h. Dr.

'investigated 1

some pbysiological effects of stimulation in the dog. It is known, on the basis of Dr. work with rats, that septal stimulation produces a deceleration in heart rate while bypotbalamic stimulation usually produces acceleration. Precise location of the electrode withis the ares in question'is critical in deternining the magoituce and sometimes the direction of these changes. Three &ccs vere implanted: electrode plscements vere in the dorsomedial nucleus of the hypothalamus, ventrozecial nucleus of the bypothalamus, and the field of Forel. The deta recorded were beart rate, blood pressure, and respiration rate durine 5.min periods of selr-stituletion alterneted vith 5-min periods in vhich lever pressing

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produced no stimulation. An exteroceptive stimulus vas correlated v!th the stimulation-available condition.

All three dogr showed transient hypertensive states during self-stimulation. Heart rate increased in all three does, and to a statistically significant dcgree in two dogs. Exercise es a factor in the cardiovascular changes vas evaluated by paralyzing two dogs vith curare, providing for artificial ventilation, and stimulating manually. Under those conditions, the blood precsure changes persisted end heart rate changes were reduced in magnitude.

A parasympathetic blocking agent, atropine, did not affect self-stimulation behavior; por did it affect heart rate or blood pressure. An adrenergic blocking agent, dibenzylene, completely blocked the blood pressure changes but accentuated heart rate changes. Another such agent, dichloroisoproternol (Dci), also accentuated heart rate changes during self-stimulation. Neither adrenergic blockine agent affected self-stimulation rate. Tbe doseges used were: atropine, 0.l pg/kg; dibenzylene, 5 mg/ke; DCI, 3 mg/kg.

5. Several experiments employing pigeons as experimental subjects vere performed. The experiments are relevant to

several problems in the analysis of behavior.

a) The principle investicotor had previously denonstrated distinctive changes in response rate durinc a relatively brief stimulus preceding a chance from one variable

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interval schedule to anothcr where the two variable interval schedules ere characterized by dirferent frequencies of reinforcement. An increase in response rate vas obtained during the stimulus vhich signalled the unavoidable transition from a high frequency of reinforcement schedule to a lower frequency of reinforcement schedule; a decrease in response rate was otteined during the stimulus signalling the opposite transition. The tvo rete changes, therefore, vere obtaired on dirferent baseline schedules. Ihe ratechange fincing wes replicated in a control experiment designed to obtain both rate changes(in opposite directions) vith reference to the same baseline schedule. A variable interval schedule of two minutes (white response key) alveys preceded. a transition to a variable interval schedule of 30 sec (green key) or 15 nin (red key). Whether the 30 sec or 15 min schedule would follow a particular exposure to the two min variable interval schedule was not predictabie unti1 the onset of a distinctive stimulus, tuc min in duration,'which preceded ench type of transition. Food was used as the reinforcer in this expericent. The results indicated clearly a tendency for the pigeons to increase response rate on the 2 min variable interval schedule during the stimulus signalling the transition to the 15 min variable interval schcdule; a rate decrensc was in evidence during tte Btimulua signalling the transition to the 30 sec variable interval schedule. Thess results

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clarified the previous finding by denonstratinz thet the two rate chances (in opposite directions) did not depend . for their occurrence on different baseline frequencies of reinforcement and response rates. Both changes vere obtained on a veriable interval schedule of tuo sinutes in the present experiment.

b) Experiments wbich study stimulus control, 1.e., the process whereby stimuli gain control over behavior, typically employ environmentel stimuli such as sounds and lights-- stimuli external to the orgenism. The concept of proprioceptive ctimuletion emphasizes .stimuli intercal to the organism, i.e., stimuli

which result from the organism's own behavior. Behavioral control exercised by behavior-produced stimulation was explicitly. studied in our laboratory through the use of a novel experimental design. The pigeon was requirei to peck on a red key either a large or a small number of times. Completion of either response requirecent extinguished the red key, and it was replaced by two white keys. If the larger number of pecks vas required on the red key, a single peck on the right wbite key produced food (reinforcement);.a peck on the left vhite key produced nothing. The converse relation obtained after the smaller requirenent on the red key. Tte white key choice behavior of the pigeons was studied as the larger and smaller requirements on the red key vere

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varied. Paired requirenents of 95-5, 75-25, 65-35, 60-40, 58-42, and 50-50 vere studied. The results dcoonstrated . elearly thet the pigcons could use feedback stimuli from their own red-key behavior to control the choize response on the whitc keys. Further, as the difference tetween the two requirements vas reduced, error frequencies increesed, particularly vhen the 60-40 and 58-42 pairs vere intrcduced. Error frequencies were about 50% vith the 50-50 pair, as expected, since the pigeon could not discriminate one requirement from the other vhen the tvo. vere equal. Finaliy, it vas found thct a delay introduced betveen the completion of the red-key requiresent and the opportunity to make a choice response increased error frequencies. Tbe "meniory" runction was variable among the several birds, and the variability was attributed to the differential development of "mediating behaviors." 1.e., stereotyped behaviors vhich filled the deley intervals The results of the experiment were interpreted as demonetrating a basic similarity between proprioceptive stimulus control and exteroceptive stimulus control. c) As noted above, experiments on concurrent scheduling most often employ a COD. The COD, or change over delay, ie symmetrical in that the same delay is procraed for change over responses betveen the tvo levers in both directions of change. An éxperiment wae perfored in which asymetrical change over delays were procranecd. All conbinctions

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of CODs of 1,'3, 9, and 27 sec vere studied. In addition, the symmetrical pairs 0-0, and 1/3-1/3 sec vcre studicd. The concurrent achedules in the context of which the cODs vere programmed vere variable interval schcdules or three min. The experiment is in the last stages of cozpletion, and a separate report vill be suboitted when the data are analyzed and the experiment is vritten in a form suitable for publication.

Anotber part of the present experiment is concerned with a second method of controlling the frequency of the. change over responaer. The first method, progranming a change over delny, vas described above. The alternative method is to establish stinulus control over the change over response.. While the pigeon is vorking on one of the two concurrent variable interval schedules, the essignment of a reinforcement on the other schedule is accompanied by a distinctive environmental stimulus. Since a change over response is never reinforced in the absence of the environmental stimulus and alvays reinforced in the presence of such a stimulus, tbe occurrence of the change over response comes under the control of the environmental stimulus. The outstanding characteristic of the data is. a marked reuction in the frequency of change over responses as compared with the experimental condition involving no stimulus corfelated vith the availability of reinforcement on the other member of the concurrent schedule. These

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data are presently undergoing enalysis in deteil, and they will be reported vhen in a form suitable for prescototion.

IV. Applicetions

There are tvo general classes of application sugsested by the research performed in our laboratory. One set of epplications involves problems of a practical pature, military problems perhaps representing the most interesting and useful subclase. Tue second set of applications stems from basic research problems.

Prcctical applications can be recognized by e unirying principle: it is desired to place a living organism in a certain geography which may be too dangerous for a human. The fundamental requirezent of any Bolution to thet problem is thet the behavior zust be under constant surveillance and control from a position remote from the terrain in question. The vork reported in section IIIA of tbis report described a procedure vhich is effective in establishing and maintaining remote control over the behavior of a dog. Surveillance of the dog's behevio is no problem, provided line of sight is an acceptable restriction. The development of a surveillance system free of that restriction is primarily an electronica problen. Possible uses of the controlled dog are not difficult to formulate.

A. A dog may be used as an amunition and message carrier over terrain too dangerous or, for sone other reason, inaccessible to man.

B. A dcg may be used as a "guided missile" in destroyirg sall, strategic structures. In this case, the dog vould carry explosive charges which can be detonated from a distance by means of a

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radio signal.

C. A dos may be used to carry sensins devices vhich detcet radiotion or chenical agents in conceotrations potentially haul to troops. By this means, a terrain nay be eveluated prior to actual occupancy. An elegant development of this application vould involve the use of the dog's physiology as the sensins instrument. Heart rate, blood pressure, etc.,vould be monitored and telemetered to the home base.

D. A dog under good behavioral control couid serve as a scout dog, or, in old cavalry terms, "ride point." A dog trained to detect and signal the presence of eneay troops would serve to prevent ambush.

Some of the above applications involve destruction of the anizal; all of the applications rish loss of the animal. One advantage f the control system we developed is the relatively snall investment in training time necessary to prepare a dog for some of the possible applications. As stated earlier in this report, about 15 hours of vorking time are often sufficient to obtain a usable dog.

Besic research applications involve the removal cf a restriction often faced ia behavioral experiments. Extended daily experizental sessions are impractical in the behavior laboratory because of satiatior effects when food is used as the reinforcer-for the behavior under study. Special techniques employing"second order schedules" have recentiy extended tbe permissible seesion length. Application of second order schedules for prolonged observation of food-meintained baselines is promising and will come into use as morc is learned about

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the dynamics of such schcdules. The advantage of revarding brain stinulation may be realized in the use of the pore comon, first order schedules. Electrode placements which do not yield edaptation or "satiation" effects may be used in studyins the long-tcrt effects of druga, radiation, etc.,on simple behaviors. Additicnal basic research applications are easily devised in many areas or bio-pedical research.

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2.

b.

5.

6.

7.

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V. Fublications

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9.

20.

11.

12.

13.

14.

15.

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VII Papers Rend at Scientiric Meetings 1.

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VII. Previous Reports In this Series

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.VIII. Distribution ilst for this report 15 copies

20 copiea

1 copy

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Rumning Head: Preparetion of the Dog for Selr-Stimulation

Corplete Address:

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A PREPARATION OF DOCS FCR SELP-STIMULATTOH OP THE BRAIN

[PAGE 106]
ABSTRACT

A detailed description of the surgical procedures involved in the preparation of a dog for selr-stimulation 1s presented. The autbors emphasize the preparation or the tip of the stimulation electrode and the preparation of the leads so thet no vound is left on the dog's beed. A description of the electrical and general behavior cbaracteristics of Belf-stimulation are included.

Indexing Itens:

1. Physiologicel Psycholocy.

2. Experimental surgical procedure.

3. ·Self-stimuletion la the dog.

4. Brain-stimuiation in the dog.

5. Electrode implantetion.

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Investigations o iotracranial stinuletion in the dog in our laboratory have encountered tvo rajor problens in the surgical preparation: 1) electrodes placed in areas vhich vhen stimuleted . support operant behavior in other species would not produce berpressing for self-stimulation in the cog. Also, 2) the electrode pedestal cemented to the skull vould loosen during the anizal's gereral activity in the horc cage. This paper describes the tectniques developed to overcome these dirriculties.

Preparation of the electrode:

The electrodes used vcre obtained from Plastic Products Corp. and are nade of bipolar twisted .Oio inch insulated platinun wire. The vire is tent to the position shown in-Fig 1 and cut to 40 . of vertical length. Using a needle the poles of the electrode are untvistei so that a gap of l.5.to 2 mm. is formed. The electrode is grasped vith a hemostat vhich is pounted in tbe electrode carriage. Plncing the point betveen the electrode poles on the mid-line and equiciotaat fron the:tuo.ear bars givessa esfereace: zero from which coordinntes pre. measured.

(Figure 1 about bere)

Surgical Procedure:

The dogs are routinely pive 1/4 grein Morphine Hydro chloride 45 minutes prior to surgery. Deep surgical anesthesia is accomplished Litb Pentobarbitol. After routine suraical preparation of the operetive fields over the bead and shouldere, a longitudinal skin incision is

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Surgical Proçedure: (cont'd)

pade over the inplantetion site. The skin and subcutaneous tissue are reflected and the periosteum is elevated. The exposed bone is pov marked vith a scalpel at the desired coordinate (anterior-posterior and lateral) positions. A hole is drilled vith a dentnl burr sufficiently large to ellou passace of the electrode into the brain tissue vithout deflection (about 8 mm, in diameter). The dure is nicked vith a Crsef Cotorcet Knire cid after fiozl chéck of the toordinate distances the electrode is lovered to the verticle depth desired.-Stainless steel screws 0-80 x 1/4" are placed around the electrode and crainoplastic cezent is applied. Sufficient cerent is edded to inciude the screvs and the electrode pedestal in a firrly bonded island of cement. The electrode leads are then ettached, the adapter threeded on and a final overlay of cepent is applied. This layer is sufficiently thick to thoroughly vaterroof the adapter-pedestal connection, to fix the polyethylene lead and to form e smooth surface (see Fis. 1).

A stab vound over the sbouiders is made and a Rurel f2 thoracic forceps is forced anteriorly through the subcutis until it exits in the implantation vound. The cistel end of the lead is grasped vith the Jews of the forcepe and vithdraval of the forceps positions the lead subcuteneously exiting as the shoulder. lounds are closed in a routine manner. The distal end of the leads are attached to a

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Surcicel Procedure: (cont'd)

comnercially availeble dog harness.

The placenents vhich bave been most successful vith respect to reward characteristics have been those aired at the inferior portion of the fornix at the level of the hypothalamus. The folloving coordinates were used as read from ) Anterior 20 mm., Lateral 2.5 m., Vertical 7.0 mn. above instrunent zero. Histological exarination of various dogs hes shoun that the electrode tips vere in 1) the fornix, 2) the camp1 Poreli and. 3) ventralmedial bypothalamus.

Stimulation Characteristics:

Electrical: A 100 cycle sine vave vith E00 uA - 2000 yA pegk to pepk acplitude procuces.strong revard cheracteristics. Resistance of the tissue varies enong dogs and is fror 6 to l2000 ohas. Hovever, it is very constant during stimulating sessions and across cays. On a square veve vith a 200 ysec pulse vidth a 200 usec interpulse tire (1.e. 100 cps, see inset, Fir. 2) a peak amperage of about l000 uA is necessary. Train duration used isa functicn of schedule and individual aniral, the rance of effective duretions is .2 to .5 of 8 second.

(Figure 2 about here)

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Behavioral: Figure 2 presents cumulative records from the lever-responses of a becgle prepared in the above manner. At first, the animal is trained to lever-press for inediate etimulaticn. Then the ratio of responses tò stimulatiorsis fixed at higher values. At fixed ratioa of 120 presses for each stimulation the dogs will vork steadily in long sessions (5-8 bours), but vill eventually shar brecks from responding of 10 to 20 min in longer sessions.

In contrast to techniques such as described by vhich anchors a protruding pedestal to the skull. this preparetion allows the scalr to completely beal end leaves no protrusions. A procedure for implanting electrodes in rets has been described by

leaves a pecestal protruding. As they describe, the healing of the ccalp is fairly corplete in the rat and, therefore, the procedure is very satisfactory. Rowever, in the dog this procedure leaves an oren vound, and a preparation vulnerable to damage frop the vigorous ectivity of the animal.

If the investication requires no tore then shree e?etirodes the procedure is convenient. Rovever,

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Discussion: (cont'd)

if zore electrodes are needed the necessity of attoching more adoptors and of passing them posteriorly to an opening et the shoulder becomes cumbertcre.

Also, the preparation of the bipolar electrode with the unusually large gap has limited use in certain research. When the purpose is to stimulate e reletively large aree in an effort to present stimulation which has reward properties, the described procedure is recommended. Hovever, when stimulation of a precise point is intended the field between the electrode tips vould be prohibitively large.

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ir

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120
80
09
40
20
0
5 Lこ!!
F-.…

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FIGURE CAPTIONS

Figure 1 Corpleted preperation of the electrode placement.

Figure 2 Cumulative records of lever presses under different fixed ratios (FR) of lever presses to stinulations.

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