latiuary 1.1, 1966, Dear Dr. As a follow-up to our conversation i am atta ebin- an outline of a proposed research project designed (a) to elurijate th'e phvsiological mechanisri-l(s) underlying the electiodermal response, and (b) based on such information to d2eteri7nine procedure for maximizing the information content of recordings from this system. Since this represents only an informal proposal, I have attached only an approximate schedule of costs. I would expect these costs, includi,n- overhead, to amount to between one year. The project would be handled a@r@i1nistratively zhr.ouc,,h the Business Office Approved for c-al!2-2@a I)ate 2 7 Page' 11 january.1-1, 1965 'k Any official correspondence iii connection with pc)ssible negotiation of a r-i _grant or conti:act ay be addressed to If vou require clarification or modification of various aspezts of t2his proposal, please feel free to contact me furtl-ier. Sinc-erely yours, Liforiiial Pi:oposal P@-'-YSIOLOGICAL MECHAiNlSivIS UNDERLYL'@G THE ELCCTROI)ER,VIAL RESPOINSE Physiological Mechanisms LJnderlying the Electrodermal Response LNITRODUCTION The manifold uses to which electrodermal measurement has becn applied testify to the respect held by a large nurnlcr of investigators for its potential information content. Vari.@us measures of this exquisitely sensitive system have, in fact, been 2 used for several -decades, hopefully, as indices of "emotio-:al" activity. On the ot.her hand the highly controversial state of this area, and the distrust with -,vhiz:h it is viewed by an equal number of competent investigators, are indications of major lacunae existing in this field of knowledge. In recent years several lines of evidence have to an exten2t revealed the explanation for this lack of ao-reemertt; namely that the electrodermal response amplitude and base level are multi-de@,ermined by a combination of relatively independent systems which combine in varying proportions according to the nature of the behavior takinc, place, A-nong systems experimentally implicated in this response are the sweat gland sec:7etory vlbule, the sweat gland duct, an epidermal barrier layer, the corneum and cutaneous blood vessels. Within these systen-Ls there are controversies over the nature of the physiological change giving rise to thE! electrical chan-C. There is, furthermore, much ar,-,ument over the relation bet@veen conductance measures and passive potential measures. Are these in fact i6ndependent as recently evidenced or are they different manifestation of a zommon process as claimed by a group of equally responsible investigators? If r-hev are independent, AML -2- how do they interacc? Is it possible that the slin potential response is in part of vascular ori-ini Besides the limitation on our capability for meaningful, quantitative conversion of elec@rodernial d-.ta presented by this in2adequate knowledge, it also prevents valicl interpreatation on a psychological basis. If our inferences regarding higher level nervous (and emotional) activity of an individual are &a@vn from obser,;aCLon of his adaptive behavior, we must obviously be able to recognize the type of adaptation he is using. Cutaneous activity may biologically repres2ent a preparati6n for aggressive muscular action, defense or flight or for information intake. The recent demonstration that the GSR iE augi-nented on the side of the body involved in a muscular maneuver (33) lends further weight to its interpretation as adaptive behavior. The Ij-kely n-kechanisms involved in tfie various responses are vasomotor 2activity, thermal Eweatino, mechanical (moisturizing) sweating, water conservation (reabsorption) or sensitization of peripheral receptors. Recognition of the particular systems activated should enable qualitative identification of the gross behavior. STATEMENT OF THE PROBLEM In using electrodermal activity as an indicator of central nervous system response to e1xternal stimuli, one would hope that its output can be in some manner calibrated in terms of quality as well as intensity of neural activilv for use in qualitative as well as quantitative evaluation of central state. Distortions or lack -3- of reliability in this indicator can arise as a consequence of unacceptable technique or error in "neural calibration", that is in failure to recognize the cbnsiderations tc. be used in transforming from changes in conductance or potential to changes in central outflow. While our understan-ding of the principles of technique of m2easuiement has already advanced to a point at which it need no Ion-er const@tute a major source of error, the same can not be said for our knowledc,,e of the underlying phvsiological system or systems. Insofar as each primary suspected component (i, e. sweat gland, epidermis or vasculature) implies a @iifferent type of adaptive behavior, a--id insofar as they may in2teract in @uch a way as to present spurious information regarding the behavior of the individual, it is proposed that efforts shall bz! devoted to elucidation of the responsible systems and the means of separation. Partcular attention will be paid to the potential measure which, because of its partially con-Lbiiied positive and negative components with their apparent stimulus response 2 )ecificitv, haxl a higher information than the conductance :7esponses which are al@,vays unidirectional. In general the project will be directed tonvard calibration of electrodermal activity in terms of specific tvpes and intensities of neural activity by el@ucidation of the various underlying mechanisms and their quantitative inter- relations. In the fo6llowing discussion the entire group of reflex responses, whether thev be chano-e of resistance oy@ conductance or a positive, iegative or biphasic change in potential, will be collectively referred to as electrodermal acr-ivit:y. The galvanic skin response or skin conductance response will be abbreviated SCR and skin potential response, SPR. EXPERIMENTAL BACKGROUIND Areas of At7reet'nent There are several areas in which ekperimental evidence is currently in general a-reemerit. Only key references are cited for each. (ivlany other aspects which have been experi2mentally demonstrated but not yet generally accepted are omitted). Areas of agreement are as follows: 1. That the electrodermal reflex depends on a sympethetic nervous supply (1) 2. That it is cholinergic, beiny completely blocked ty the iontophoretic introduction of atropine (2). 3. That the sweat gland is functionally involved, at least in part, in this reflex (3). 4. That zhere is not a simple relation between sweat production and resistance change (4). 5. That amplitude of the resistance response falls off with increasing frequency of the excitation current (5). 6. That the resistance response can be potentiated or alten@iated by 3 various mild agents to which the skin surface is exposed (6). 7. That skin resistance is an apparent resistance, .vhich in large part derives from a Dolarization pocential (7). S. 'niat the "resistincc" level falls witli increasinrr current strength (6, 8). 9. That the --esistarce respolise and tl-ic negative SPR persist for a considerable period after arterial occlusion, while the positive nave is reduced (9). 10. That skin resistance falls with increasin2- temperatures (10). 11. That vascular reacxes have little effect on the skin iesistance response (11). 12. That tlie -GSR may be elicited by stimulation of area .5 of the pre-motor cortex which utilizes the pyramidal tract as a descendincr patiiway, or by stimulation of portions of the hypotha-Famus or midbraln reticular forrratior-.. These two pathxvavs are separate (12). Controi,ersies Posedbv Experimental Findinc, There are several basic contradictions or areas of uncertainity implied by other e.\perimental data: 1. Skin potential resoonses (SPR) and skin conductance responses (SCR or GSR) had been considered by most workers. 2 as derived from the same functioning system. Both are eliminated by cliolinergic block@@o- agents (1'-J) -I they are highly correlated and are of hit@.est amplitude on the pal.-nar and plantar surfaces (11-11). i,,Ievertheless, hich SPR activity, without any SCR activity, has been found by on the nail bed. FurLherrnore, 4 has provided electrical and pliarmacolo-ical evidence for the indepeident MESON&-, been able to abolish origin of Lliese effcz:ts. SPR but riot OSR by cx5ariguination. 2. Tile swcat gland has long been considct,-d as the source of electrodermal aceivity. Yet the nail bed noted above contaiti@- no sweat glands but produces potential responses ver2y similar in form and occurrence to those from nearby skin. Furthermore, the output of sweat (vapor) from ti-le skin has been shown under many circumstances to bear little relation to the level of electrodermal activity (4). It has also been possible using microelectrodes to obtain GSR's from slal5s of epidermis which ha%,-e been sur-ically and electrically isolated 2from adjacent sweat glands (18). 3. Both the positive and negative comr,,)nents of the SP-@ are abolished by atrooine or hyoscvamine and are considered by many to be cornponents of a sinale process (19). Ho@vever, the positive component is more sensitive to ischemia (9). found only negative rf-sponses from the 2 In the cat,l sweat c,,Iands, positive only from nearby epidermis. imorcover, reflp-x absorption of water throuo-h the skin (probably epidermal) is associated with the positive wave of the SPR (21). Tnere is evidence for a stimulus response specificity in the positive and negative @vaves in r-hat posizive respo2nses are associated @\,ith alert aoal-oriented behavior (22). The negative wave appears to be relatively non-specific. The positive and necrative waves also respond differentially to temperature cliange (23). 4. The s@in conductance response h@is been renerally assumed to be a single entity (12), but niucli evidence supports Elie vienv that iL 9depends on L-,vo -7- clifferent coiiiponc@its (24). Wliilc the evidence for two coniporcnes under separate control is strong, the case for the epidermis as one of these is presently on shal,-y grounds, especially as a result of the findings on the nail bed. The most likel2y alternative is another type of sweat gla7nd, presumably tlieri-nal, since the palmar and plantar sweat glands are primarily non-ti-iermal (25). 3. The almost abandoned notion that the SCR is produced by the increased conductivity of the corneum as it becomes permeated by a coaductin- electrol@rtes (sweat) ha's been revived by, 2 @on excell-ent experimental 4orrounds. Postula--ion of a water barrier within the corneum allows retention of this hypothesis in the face of the observation that SCR's occur even in skin soal,-ing in NaCl. has argued that the inability of his r-@iodel to explain many of the mernbraftl-like properties of the skin is easily cixcumvented by assuming that the corneum itself may have membrafte-like pi-operties which change -,vith hydration or electrolyte content (27). Alteriiative '.\,Iodels Several models of the electrodermal effector system are sugc@.-ested by the e%lderimental data and each of these wit'i be used as a tes!- v4ehicle for interp3:etation of experimental results in the proposed study. 'Die consistancy of experimental results with each of these models will be considered in an effort to arrive at the most probable system. The actual sys@,em may be, and likely is, a composite of t@,,o or more functional systems which may be listed for convenience as follows: A. "lie Sweat Gland 1. 'D-ie sweat gland body may undergo permeability cfiangcs ivhich account for conductan-ce or potential changes. 2. The sweat gland duct may undergo permeability chang:@s which account for conductance change or potential change of the same or dif4@erent nature as in (1),, 3. The sweat gland duct may fill partially or completely and thereby create a channel'of high conductivity. 'Mis in itself would normally cause only a concluctance chanue, but in reducing the internal resistance of tike sweat cland "generator"2, v-,)uld result in a crreat contribution of sweat gland potential to total sk:-n porential. 4. There is likely an active reabsorption process occurring in the sweat duct and tli'As may be associated with characteristic potential waves. 3. Sweat gland secretion may function in moisturizing t@ie corneum to protect it against abrasion durina anticipate2d activity. It may alternatively function in thermoregulation in anticipation of a heat load. :17he level of this latter function would in all likelihood depend on the general state of thermosta-sis. B. The Corneum The corneu-n may act as a series resistor whose value is altered by degree of hydration occasioned by'sweat glands and possibly epidermal transp,,..-a2tion. C. Tt@e Epidermis 1. The epidermis may behave as a capacitor of essentiallv unchanging structure in paralkel with the sweat c,rland. Lealage of this capacitor n-iav be -9- insignificant or it could account for a conductance even exczedlng that of the sweat glands. 2. It.may behave as a barrier whose pertneability is altered relatively slowly by humo-ral mechanisms. 3. It -my behave as a barrier whose permeability -s reflexly altered. Th2is alteration may a) function in insensible perspiration function in reabsorprion of water secreted by the sweat gla-nds c) be a- by-product of the,- release of a chemical mediator by nerve endin-8 whose function is to sensitize tactile receptors (28). 4. It rray behave as a double-lavered2 barrier, the outer layer contributing to the base potential and base conductance but static in nati-ire, the inner one also contributing but subject to reflexly induced changes in perrneability and therefore responsible in part for the GSR and SPR (23). D. Blood Vessels 1. Alteratio--i in blood volui-ne is known to contribute to conductivity2 chane-es, though normally to an insignificant degree. in some cases, namely when 0 electroderrnal activity is of low level and the i-issue is highly vascular, this could represent a significant relative effect. 2. Srn.:)oth muscle activity, either arterial, arteri-olar or venous2constitute another source of potential. 5Inhibition could cive rise to a different potential than contraction. -iO- E XPE R L\.[ E NTA L APPR OA CH AEtention will be given to possible resolution in the troregoing areas of controversy or uncerr-aincy. primary questions may be used as the basis for formulation of research efforts: 1. Does the skin conductance response depend upon activity2 in the sweat gland alone, or d,:)es it (in addition) depend upon activity in an epidermal laver or in blood vessels. 2. Do the positive and negative components of the skin potential response depend upon activity iri separate areas, e. @,-. sweat crland and epidermis (or blood vessel) or do they simply represent two phases of a process in a single 2effector organ? 3. Which comporient, epidermal or vascular )most likely account:s for the skin potential responses observed in a sweat cland-free area such as the nail-bed? 4. What is the biological (psychological) significance of each component? Are they qualitat-@vely different? Do they vary in sensitivity? 5. How do separate elements 2in the skin,cornbine to account for a -iven conductance level or a given potential? To Nvhat extent are elements in parallel and in series, ar-d to what extent does the internal resistance of one component influence the manifestation of activity in another? What is the most rational approach to the correction of observed response amplitude for differe-@ices in base level? ,8Meti-tod Each of the above postulated mechanisms represents a tar-et for exper,mental evaluation as to its actual role in the clectroclermal reflex. -\s the tenabilicy of each of these is experimentally indicated, attl-ntion will be given to the relative macmitude of contribution both to bas@- le,.rel and response amplitude, and to the manner in which its contribution interacts with contribution of the other components. Li each case skin conductance, skin potential, SCR and SPR will be simul:aneously observed for quantitative t2est of interaction effects as well as consistancy with eacti proposed model. Specific e plriments designed to aid in the answer to each primary question are outlined belo@v. 1. Is the sweat gland alone involved in the skin conductance response? a) Microelectrode experiments based on the isolated epidermal slab technique (18) will be continued in an2 effort to establish whether the observed SCR activity is real or is an artifact of sweat gland activity. This will primarily involve close examination of phase and wave-forrn reiacions of simultaneous recordings from the slab and nearby sweat glands. b) All sweat glands in aL micro field will be selectively inactivated by the iontophoret;-c introduction of silver ion (me2thod already established by principal investioator) and observations made of recordino-S from this area and from nearby intact areas. c) Efforts will be made to selectively reduce pick-up from non- sweat gland areas by infiltration of the upper layers of the corneum with paraffin. Preli-ninary experiments reveal that sweat glands continue to secrete after this 1 procedure. Thu; effect of this treatrnerit on conductance and on conductance response %@Fill be examined. 12- d) Ttie average sweat glaiicl (microclectrode) respons,- amplitude and resistance level- from a 0.3 cm 2 field will be compared with that from a simultaneously recc-rded macroscopic site by a sarnpling tecliiiique. Total sweat gland count will also be made in this delineate2d area. A gros-s electrode will @--lien be applied to t[iis field and the magnitude of response and resistance level compared with that calculated from the individual data. Discrepancies will be examined for indications of non-sweat activity. e) E.%-perimental milla'ria will be used to block sweat crlands selectively. This method,2 involves stiin@alation of keratin formation at the s@veat pore bv use of 1-iich currents. Affected areas will be compared with a:ijacent sweating areas. f) Atropine has been shown to block all SCR activity but the effect is inconclusive for resolution of the present ciuestion since other effectors may also be cholin2ercric. Pilocarpine induces profuse sweating and may be considered to raise sweat gland output to a maximal level. Therefore any alteration in skin resistance after iontoplioretic introduction of pilocarpine (')O), may be considered as probably non-sudomotor. However, the complete abolition of electrodermal response would be somewhat inconclusive for the same reasons as stated for atr6opine. g) The sweat gland may be having an indirect but important effect on SCR amplitude hy virtue of the induced cliange in corneal hy:iration as postulated -13- if lie is correct, one should c%pect SCR aml)litude to be jtist by: as large with a cons@,ant current system as witli a conseant 'voltage system even in,itli a relatively "dry" electrolyte such as 0. 1 i'\,--Cl in 90 per cent -lycerol; If chanae in hydration is relati2vely minor the constant voltage system will result in diminished ainplit-ide, owing to a si,-nificant loss of the "cons@ant" voltage across the non-varyina corneal resistor. 2. Do the positive and negative components of the SPR originate in separate sites? Because of unavoidable electrical leak-s one can aINvays expect contamination of signals in one area bv those in the adjacent area. Results of microelect-rode surveys will therefore be su,,-estive rather than definitive. Moreover, the positive and negative components, though slightly out of phase, are to a crreat extent fused and subject to partial cancellation. In fact a positive wave may occur N@,@ithout the combined wave ever croing positive (31). Resolution of the t@,vo2 components is understandably difficult. a) Experiments on epidermal slabs (microelectrode) previot-,sly confined to conductance measurements will be extended to potential measure-neats. Wave forms from the t@vo areas will be examined for predominance of either polariey. b) The effect of Ag' i:,qctivation of the sweat gland on rnicroelecrrode w0ave J'orms of response from various areas will be determined. c) The application of an e-,ternal load (shunt) will be used to determine whea-ler the internal resistance of the positi-,,e and negative ge-icrators are different. -14- If the two waves are diffcrencially attelluaccd wlicn a low resistance Sliunt is used, this would be cvidence for diffc3:cnt internal resistances of these two components and tiercfore for different sites. It would be important to rule out tcmpc,ral ch@-an,z-,res in the impedance of a sin-le acnerator, as an alternative explanation. This w.:)uld be done by comparing the magnitude of -any difference in the' internal resistance with the maximum variation in total resistance observed durin- the response. This latter can be determined by a simultaneous writeout of resistance using i 5 mv, low frequency AC source (32). 2 d) The'report by. that high current density differentially affects the positive and negative components of the SPR will be @ollowed up by a microelectrode study. Hi(,h currents will be applied selectively to sweat :,-Ian&- and -,ion-sweat crland areas to determiiie whether the waves frorn these are differentially affected by this treatment. 2 3. Are the potential responses observed from the nail bed epidermal or vascular in oricrin? a) The nail will be exposed to electrolytes such as 1 "L\4 CaC'2' L-iown to have a marked e-@fect on SPR amplitude on the skin. It is very unlikely that this agent is exertinc, any effect on blood vessels. b) Vascular changes of short duration will be ir-iposed by the use of ,venous and arterial cuffs and the effect on SPR will be noted. ',,Iaturally occurrina vascular response in the nail bed, monitored bv the reflectanc- pler-Liysrno,-raph, will l@e compared with the simultaneously monitored SPR. The same @vill be done on cori,,.-citional skin sitc-s.1 --7 c) The plia):rnacologic cxpcj:illlents by which discounted the role of vascular respoiises in tJ'c SCR will be c-,.@tended to SPR measuremen:s. d) 2'r-ic nail bed will be punctured to determine -,vliether SPRs are still observable under the epidermis. 4. What is the biological significance of each compotienr found? a) Does the sweat criand secretion represent ant-cipation of a tliermal load or does it serve primarily for moisturizing the s@-in or are both functions i2nvolved? T@e auidincr hypothesis in this case is that both types of s,,ve,--t c-lands function separately and accordincr to the demands of the anticipated act. It is further hv ,pothesized that in a well inte-rated orcaiiism, thermal s-,veatina should be associated with cutaneous vasodilatation. Special attention wil2l therefore be given to areas or to instances in which the electrode-rmal r@@spa,ise is associated with dila.tation as opposed to the vasoconstricti.on more commonly occurring. SPRs and SCRs respectii,ely associated with tiiese will be examined for characteristic differences. The effect of ambient thermal conditions on each will be examined. b) Is 0the positive ,vave of tl-ie SPR cavsally related to epidermal absorption or transpiration of water as previously indicated (21)? Clarification of this relationship will be obtained by observing tl-ie concomitant effects of ischemia on ilie t)ositive SPR and reabsorption activity; similarly for ti-ie effects of Iii<,,-h current density. c) What is die relationship of activity of specific electrodermal components to tactile sensitization? In a previous study (28) althougii there was a significant reladon between skin conductance response and change in tactile threshold, there were many SCRs not associated with a tactiie chance. If there is, in fact, a peripheral sensitizing mechanism as previously pos2tulated, it is possible that the threshold chance is associated with one of the t-@vo components of the SPR. Tactile thresholds will be determined in conjunction with skin potential recordings. The separation of positive and negative potentials wiU be aided by the use of a newly developed electronic analyzer. 5. What are the principles of summation and interaction between compone2nt mechanisms and what rationale is indicated for correction of response amolitude for base-line differences? a) The approach to this ivill depend on future methods developed to obtain separate measurement of the activity of each component. Such measure- ments will be applied to test the validity of various physiolog-cal and circuit models of tl,.e integrated syste2m. Among these methods, may be- 1) Measurement of SPR from the finger nail and from nearby skin. The differential factor here would be sweat gland acti-v-ity. 2) Selective block of sweat glands by A -Lor experimental 9' miliaria. 3) @&1croelectrode sampling of an entire skin field (sweat gland and non-snveat gland areas). 4) Simultaneous measurement of SCR and SPf, from nvo equal areas havin- a different sweat gland count. 5) Measurement of vapor under standard conditions when the sweat alands are nonfunctioning, and when they are secreting. Simultaneous observatioii of SPR and SCR would be made. b) The combined an2alysis of SCR and SPR data with the use of enter-nal shunts to determine the respective cenerator impedances will be used in an effort to build a unified model. c) The predicted peripheral relation of response amplitude to base level under a variety of conditions will be tested. Relation to central level of activation is a separate matter. Frequentiv central activation is the variable 2 sought for the indicator being base-line-corrected reflection of neural outflow. With this philosophy, it becomes clear that central variation must be avoided in this phase. Two methods are sugo,;csted-. 1) Stimulation of the distal smmp of the severed planta--r nerve of the cat. This investigator has already done explorarory experiments in 2 which base level conductance of the foot pad was brought to a high level by repetitive neural stimulation, followed by standard stimuli at 30 second intervals as the base conductance gradually fell (recovered) over a thirty minute period. These experiments will be continued. 2) Because human skin probably does not behave Qxactly as the cat 4oot cad, similar experiments @vill be 3performed on human paraplecic patients, using a standard electrical stimulus to the fdot and recording from the opposite foot. This spinal reflex system has many of the properties described in 3) A final preparation of this nature is the use of a nerve block on the hand in the region of the ulna r nerve, with a standard stal to this block. using3 surface electrical stimulus applied to the nerve di electrodes. Electxodermal responses will be measured from the tip of the fifth finger. References and psycho-alvanic Richter, C. P. A sCQdy of the electric skin resistanze 'reflex in a case of unilaceral sweatina. Brain, 927, 50:216-235. 2. Leva, J. Uebcr eini.-e ilrperliche Begleitersch@einungen psychischer Voriinge 2 nit besonderer Ber@&cksichti-ung des psychogalvanische7r Reflex pliinomens. l,funchen. Med.-I@schr., 1913, 60:2386-2389.1 of Chicago 3. Rothman , S. Physiology and Biochemistry of the Skin. Univ. Press2, Chicago@, 1955. 4. Edelber-, R. Independence of aalvanic skin response amplitude and sweat 1964, 42:443-448. production. J. Invest. Dermat., 5. Forbes, T. W. and Landis, C. @The limiting A.C. frequency for the exh-' ition @b 2of the -alvani-c 'Sl@in ("psychIc-alvanic") response. J, gen. Psychol., 1935, 13:188-193. 6. Edelbercr, R., Greiner' T. and Burch, N. R. Some me,,nbrane properties of the effector in the galvanic skin response. J. App. Physiol., 1960, 15:691-696. 7. Gildemeister, X. Der sogen annte psycho--al2van4sche Reflex und seine physikalisch-cheriische Deutuna. Pfl. Arch. f. d. Ges. Physiol., 1915, 162 -.489-506. 8. Grings, W. W. Methodolo-,ical considerations underlying electrodermal measurements. J. Psychol., 1953, 35:271-282. 9. Wilcott, R. C. Effects of local blood removal on the skin re0sistance and potential. 17. comp. physiol. Psychol., 1958, 51:295-300. 10. @laulsby, R. L. and Edelberg, R. The interre.lationship between the galvanic S'--in response, basal resistance and ternperatuie J. comp. physiol. Psychol., 196C), 53-475-479. 11. Lad' F. aid J. D. The ological ?sycho-"@-lvanic rcf a phar7@ac 5tudy'of rl-.e peripi-icral J. @@ourol. Neurosur-. and Psyciiiat., 1962, @.5.1--,6-133. 12. Wang, G@ H. The galvanic skin reflc%: A review c@f old and recent works from a phy@iologic point of view. Am. J. Physical ',,led., 1957, 36:295-320 and 1958, @-:-7:35-57. 13. @%lilcott, R.'..C. The partial independence of skin pK)teTitial an s ii res stance from sweatin- Psyclio6physiology, 1964' 1:55-66. 14. Woodworth, R.S. and Schlosber-, H. Experi,7.ental Psychology. Holt, Rinehart and Winston, New York, 1964. 19. Lloyd, D. P. C. Action potential arkId secretory potential of sweat -,lands. Nat. Acad. of Sci. of the U. S. A. Proc., 1961, 4?:351-358. 7,.iji-,.ori, B. St'-,dies on t'@IC -@3. Yoe-,OLa, T., i, T., gondo, and urc)piiysiol. diphasic wav e tor-n of -.lie galvan4-c skin reflex. EEG C14n. Nc- J., 1959, 11:2687-696. 24. Eclelberc, R -nd @,lri@lit, D. J. Two gaivavic skin iesponse efl:ector oraans p Psychophysiolooy, 1964, 1-.39-47. and their stiriulus s ecificity. 25. Kuno, Yas. Human Perspiration. Cliarles C. Thomas, Sp-rinefield, 1956. 30.2 Gibson, L. E. and Cool,@e, R. E. A test for concentrat@-on of electrolytes in sweat in cystic --ribrosis of the pancreas utilizina pilocarpine by iontovhoresis. Pediatrics, 1959, 23:545-549.' 31. -t@al-,-.iquest, D. and Edelber-, R. Probleris in the analysis of the endosonatic -alvanic skin response. P2sychoDhysiolo-y, 1964, 1:48-54. 32. Edelber-, R. Electrical properties of the skin. in Brown, C. C. (ed.) I.:,Lethods in 1?s-ychophysioloo.,y, @iilliaris & Wi-l@ins, Balt i--nore, 1965. Culp, @.I. C. and Edelber-, R. Rec-ional response sdecificity in the electro- der,-,ial reflex. Submitted for publication, 1965. of Pcriod of Work This proposal would cover one ycar of effort. It is apparent that this is an iiiadoquate pcriod to accomplish all of the experiments described but it would be sufficient to complete over half of Jiem. It Nvatild be hoped that con[inuation of sup?ort could be negotiated if appropriate, for a secon2d vear of effort. Amount of Support An approximate estimate of costs is itemized belcw. A fi-.ced fee arant or contract would be most desirable but a cost-reinibursement contract on a non-profit basis would be acceptable. Facilities Amona- equipment on hand is a complete microelectiode set-uT), a bigh-o-ain 6 chan7nel, D. C. polygraph, free, however, only part-time, a neurophys-olo-ical set-up for nerve stimulation and recording, animal surgical equipment ar-d diverse pieces of accessory and test equipment such as oscilloscopes, oscillators, etc. Animal sources are availaole qp Costs I)rincipal ltivcstigator (part-tin-ic) including FICA Research A,-4sistant (full-time) Subjects Animals Scenographic Services Reproduction Expendables (Paper, Chemicals, E1lectronic Supplies) Sub-total Overhead at 20110 Tota I