Doc 0000021807

The visible page presents a stylized graphic juxtaposed with text. The graphic depicts a metallic vault door, complete with a central dial and various mechanical components, rendered in shades of gray and illuminated with bright blue accents. To the right of the vault, white text is layered against a dark background, featuring the title "THE BLACK VAULT" in a stylized, handwritten font. Below the title, the text explains that the document is from an online database of declassified government documents and specifically references the MKULTRA/Mind Control Collection, stating it contains over 20,000 declassified pages from the CIA. The text concludes with a website address in yellow font. The page contains no photographs, stamps, handwritten annotations, forms, tables, redacted content, or visual evidence of experimental procedures or facilities. ' January u. 1966/ I /' I -~1 ·I I Dear Dr. i As a follow-up to our conversation I am attaching an outline of a proposed research project designed (a) to elucidate th~ physiologicd mechanism(s) underlying the electrodermal to response, and (b) based on such information determine procedure for naximizing 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, including overhead, to amount to between .. •' \for one year. The project would be handled administratively jlrough the Business Office . . . .. .. -· .... - _. ~· ~- .. -' I -~ Page" II " -January. U, 1965 _,/ ~~ /"< "'· ...... ./ / 1 Any official correspondence in connection with pos~ible ncgotiatiQ_~_Qf ~_gr~_Qt or contract may be addressed to - ~--.... . ---------- ,. .. / ......... If you require clarificatio/ n or ' modification of various aspe:;ts of this proposal, please feel free to contact me further. . / / . /·' ··-· .,_ ...._.,.. / Sinc~re~~ yo_~~~!__ _~ - , ... 1/ \ / / \ ~~~------------------------~-------------------------------- Inform:.tl Prvpusal PEYSIOLOGICAL MECHANISMS UNDERLYL~G THE ELECTRODERMAL RESPONSE __ ,' -··· .... ~- \ ......................... -.-"-' ·- --·. ·------- ( - -\ Physiological Mechanisms Underlying the Electrodermal Response h'\JTRODUCTION The manifold uses to which electrodermal measurement has been applied testify to the respect held by a large number of investigators for its potential information content. Varj·:us measures of this exquisitely sensitive system have, in fact. been used for several decades. hopefully, as indices of "emotio·:al" activity. On the ottter hand the highly controversial state of this area, and the distrust with whL: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 extent revealed the explanation for this lack of agreemeilt; namely that the electrodermal response amplitude and base level are multi~determined by a combination of relatively independent systems which combine in varying proportions according to the nature of the behavior tak~g place. A:nong systems experimentally implicated in this response are the sweat gland sec::-etory tubule, the sweat gland duct, an epidermal barrier layer, the corneum and cutaneous blood vessels. Within these systems there are controversies over the nature of the physiological change giving according to the nature of the behavior tak~g place. A:nong systems experimentally implicated in this response are the sweat gland sec::-etory tubule, the sweat gland duct, an epidermal barrier layer, the corneum and cutaneous blood vessels. Within these systems there are controversies over the nature of the physiological change giving rise to th= electrical change. There is, furthermore, much argument over the relation bet\veen conductance measures and passive potential measures. Are these in fact independent as recently evidenced or are they different manifestation of a ::ommon process as .. claimed by a group of equally responsible investigators? If they are independent, -2- how do they interact? Is it possilile that the skin potential response is in part of vascular origin? Besides the limitation on our capability for meaningful, quantitative conversion of elec::rodermal data presented by this inadequa-te knowledge, it also prevents valh. . interpreatation on a psychological basis. If our inferences regarding higher level nerv<?us (and emotional) activity of an individual are drawn from observation of his adaptive behavior, we must ob,•iously be able to recognize the type of adaptation he is using. Cutaneous activity may biologically represent a preparation for aggressive muscular action, defense or flight or for information intake. The recent demonstration that the GSR is augmented on the side of the body kvolved in a muscular maneuver (33) lends further weight to its interpretation as adaptive behavior. The Ukely mechanisms involved in the various responses are vasomotor activity, thermal sweating, mechanical (moisturizing) sweatingt water conservation (l:"eabsorption) o= sensitization of peripheral recept::>rs. Recognition of the particular systems activated should enable qualitative identification of the gross beh,avior. STATEMENT OF THE PROBLEM In using electrodermal activity as an indicator of central nervous system response to external stimulit one would hope that its output can b~ in some manner calibrated in terms of quality as well as intensity of neural activity for use in qualitative as weLl as quJ.ntitative evaluation of central state. Distortions or lack of reliability in th~s indicator can arise as a consequence of unacceptable technique or error in "neural calibration", that is in failure to recognize the considerations to be used in transforming from changes in conductance or potential to changes in central outflow. While our understanding of the principles of technique of measurement has already advanced to a point at which it need no longer constitute a major source of error, the same can not be The document is a typewritten letter with a date of January 11, 1966. At the top right, there is a black ink annotation, possibly a signature or a symbol. Below the main body of the text, there is a section labeled "Approved for Release" with a handwritten date and a circled number "148". Several areas of the document appear to be redacted or obscured, indicated by dotted lines or smudges, particularly in the upper central portion. There are no photographs, diagrams, or tables visible on this page. This declassified CIA document page appears to be a standard memo or letter, with the following visual elements: - **Date and Page Designation:** "Page II" and "January 11, 1965" are printed at the top left. - **Body Text:** The main content consists of typed text, appearing as standard correspondence. - **Handwritten Markings:** There are some faint, scribbled handwritten lines and marks scattered across the page, particularly in the margins and around the text. These do not appear to be significant annotations or signatures. - **No Images, Stamps, or Forms:** There are no photographs, official stamps, or structured forms visible on this page. - **No Redactions:** There are no visible redactions or obscured content on this page. - No visual evidence of experimental procedures, equipment, or facilities is present. considerations to be used in transforming from changes in conductance or potential to changes in central outflow. While our understanding of the principles of technique of measurement has already advanced to a point at which it need no longer constitute a major source of error, the same can not be said for our knowledge of the underlying physiological system or systems. Insofar as each primary suspected component (i.e. sweat gland, epidermis or vasculature) implies a different type of adaptive behavior, a:J.d insofar as they may interact in such a way as to pr~sent spurious information regarding the behavior of the individual, it is proposed that efforts shall be devoted to elucidation of the responsible systems and the means of separation. Particular __ attention will be paid to the potential measure which, because of its partially combi11ed positive and negative components with their apparent srimulus response .__,ecificity, hao/ a higher information than the conductance ::esponses which are always Wlidirectional. In general the project will be directed toward calibration of electrodermal activity in terms of specific types and intensities of neural activity by elucidation of the various underlying mechanisms and their qua_ntitative inter relations. In the following discussion the entire g-roup of reflex responses, whether they be change oi resistance or conductance or a positive, r.egative or biphasic change in potential, will be collectively referred to as electrodermal acti\•ity. .. ~ ...... The galvanic skin response or skin conductance response will be abbreviated SCR and skin potential response, SPR. EXPERIMENTAL BACKGROUND Areas of Agreement There are several areas in which experimental evidence is currently in general agreement. Only key references are cited for each. (Many other aspects which have been experimentally demonstrated but not yet generally accepted are omitted). Areas ::>f a£!eement are as follows: 1. That the electrodermal reflex depends on a symp::.thetic nervous supply (1). 2. That it is cholinergic, being completely biocked 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 ::here 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 attenuated by various mild agents to which the skin surface is exposed (6). 7. That skin resistance is an apparent resistance, which in This declassified document page appears to be a title page for an informal proposal. The text "Informal Proposal" is centered at the top, followed by the proposal's subject: "PHYSIOLOGICAL MECHANISMS UNDERLYING THE ELECTRODERMAL RESPONSE". The rest of the page is dominated by faint, unidentifiable rectangular shapes and lines, possibly remnants of a previous document or annotations. The nature of these markings is unclear, but they do not appear to represent specific experimental procedures or equipment. There are no photographs, stamps, or filled-in forms visible. (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 attenuated by various mild agents to which the skin surface is exposed (6). 7. That skin resistance is an apparent resistance, which in large part derives from a ;=~olarization potential (7). -5- S. That the '"resistance" level falls with increasing current strength (6, S). 9. That the :-esistance response and the negative. SPR persist for a considerable period after arterial occlusion, while the positive wave is reduced (9). 10. Thp.t skin resistance falls with increasing temperatures {10). 11. That vascular re(lexes have little effect on the skin resistance response (11). 12. That the GSR may be elicited by stimulation of area 6 of the pre-motor cortex which utilizes the pyramida_l tract as a descending pathway, or by stimulation Jf portions of the hypotharamus or midbrain reticular formatior:. These two pathways are separate (12). Controversies Posed. by Experimental Findings. There are several basic contradictions or areas of uncertainity implied by other experimental data: 1. Skin potential responses {SPR) and skin conductance responses (SCR or GSR) had been considered by most workers. I ' '\as derived fnm the same functioning system. Both are eliminated by cbolinergic --· blocking agents (13); they are highly correlated and are of higt.est amplitude on the palmar and plantar surfaces {14). Nevertheless, high SPR activity, without any SCR activity, has been found by on the nail bed. Furthermore, 1 \has provided electrical and pl1armacological evidence for the independent .------·--- ... -6- .--·-------~---~have been able to abolish origin of these effc;::ts. SPR but not GSR by exsanguination. 2. The swEat gland has long been considcc-ed as the source of electrodern1al acti'lity. Yet the nail bed noted above contains-no sweat glands but produces potential responses very similar in form and occurrence to those from nearby skin. Furthern:ore, the output of sweat (vapor) from the 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 slaBs of epidermis which have been surgically and electrically isolated from adjacent sw_eat glands (18). 3. Both the positive and negative components of the SP3. are abolish.ed by atropine or hyoscyamine and are considered by many to be components of a single process (19). However, the positive component is The page is primarily text, with no photographs, handwritten annotations, or official stamps. The text is laid out in two columns, characteristic of a typed document. There are no diagrams, schematics, forms, or tables visible. There are no apparent redactions or obscured content. The visual presentation is that of a standard academic or research paper, focusing on the physiological mechanisms underlying electrodermal response. from slaBs of epidermis which have been surgically and electrically isolated from adjacent sw_eat glands (18). 3. Both the positive and negative components of the SP3. are abolish.ed by atropine or hyoscyamine and are considered by many to be components of a single process (19). However, the positive component is more sensitive to ischemia (9). -~ In the cat,/ -·----:\found only negative responses from the sweat glands, positive .. ...__._.. .-- only from nearby epidermis. Moreover, reflex absorption of water through the .5 kin (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 waves in that positive responses are associated with alert goal-oriente::! behavicr (22). The neg3.tive wave appears to be relatively non-siJecific. The positive and negative waves also respond differentially to temperature change (23). 4. The skin conductance response has been generally assumed to be a single entity (12), but much evidence supports the view that it depends on two ==~~============a~----~--------~------ -7- different components (24). While the evidence for two compm:cnts under separate control is s_trong, the case for the epidermis as one of these is presently on shaky grounds, especially ns a result of the findings on the nail bed. TI1e most likely alternative is another type of sweat gland, presumably thermal, since the palmar and plantar sweat gl~nds are primarily non-thermal (25). 5. The. almost abandoned notion that the SCR is produced by the increased conductivity of the corneum as it becomes permeated by a conducting electrolytes (swe"-t) luis been revived by- ·.-lon excellent experimental grounds. 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 soaking in NaCl. /has argued that the inability of his oodel to explain many of the membra~ like properties of the skin is easily circumvented by assuming that the corneum itself may have membrat~-like pr-operties which change with hydration or electrolyte content (27). Alternative :tvlodels Several models of the electrodermal effector system are suggested by the experimental data and each of these will be used as a tes: vehicle for interpretation of experimental results in the proposed study. TI1e consistancy of experimental results with each of these models will be considered in an effort to arrive at the moat probable system. - ~!:::··=== • MIL& e -s- The actual each of these will be used as a tes: vehicle for interpretation of experimental results in the proposed study. TI1e consistancy of experimental results with each of these models will be considered in an effort to arrive at the moat probable system. - ~!:::··=== • MIL& e -s- The actual system may be, and likely is, a composite of tvo or more functional systems which may be listed for convenience as follows~ A. The Sweat Gland 1. The sweat gland body may undergo permeability clianges which account for conductance or potential changes. 2. The sweat gland duct may undergo permeability changes which account for conductance change or potential change of the same or different nature as in (1). 3. The sweat gland duct may fill partially or completely and thereby create a channel of high conductivity. This in itself would normally cause only a conductance change, but in reducing the internal resistance of C\e sweat gla!ld "generator". v·'Juld result in a great contribution of sweat gland potential to total sk::n potential. 4. There is likely an active reabsorption process occurring in the sweat duct and this may be associated with characteristic potential waves. 5. Sweat gland secretion may function in moisturizing t..~e corneum to protect it against abrasion during anticipated activity. It may alternatively function in thermoregulation in anticipation of a heat load. .The level of this latter function would in all likelihood depend on the general state of thermostasis. 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 epidennal transpuation. C. The Epidermis 1. The epidermis may behave as a capacitor of essentially unchanging structur~ in parallel with the sweat gland. Leakage of this capacitor may be -9- insignificant or it could account for a conductance even exc;;:eding that of the sweat glands. 2. It .may behave as a barrier whose permeability is altered relatively slowly by humoral mechanisms. 3. It ma.y behave as a barrier whose permeability ::.s reflexly altered. This alteration may a) function in insensible perspiration j) function in reabsorption of water secreted by the sweat glands a c) be by-product of the release of a chemical mediator by nerve endings whose function is !:o sensitize tactile receptors (28). 4. It n:ay behave as a double-layered barrier, the outer layer contributing to the base potential and base conductance but static The page displays typed text, with a page number '-2-' at the top center. There are no photographs, handwritten annotations, signatures, official stamps, forms, diagrams, schematics, organizational charts, tables, or structured data present. There are no visible redactions or obscured content. The page exclusively contains text pertaining to a research topic, likely from an academic or scientific paper. The provided image is a scanned page of a declassified document. It contains typed text, with no photographs, handwritten annotations, or official stamps visible. There are no forms, diagrams, schematics, organizational charts, or tables present. The page is clean and appears to have no redactions or obscured content, and there is no visual evidence of experimental procedures, equipment, or facilities described within the text. of water secreted by the sweat glands a c) be by-product of the release of a chemical mediator by nerve endings whose function is !:o sensitize tactile receptors (28). 4. It n:ay behave as a double-layered barrier, the outer layer contributing to the base potential and base conductance but static in nature, the inner one also contributing but subject to reflexly induced changes in permeability and therefore responsible in part for the GSR and SPR (23). D. Blood Vessels 1. Alteratio:t in blood volume is known to contribute to conductivity changes, tboug"h normally to an insignificant degree. In some cases, namely when electrodermal activity is of low level and the tissue is highly vascular, this could repreaent a significant relative effect. 2. Sm:)oth muscle activity, either artenal, arteriolar or venous, constitute another source of potential. Inhibition could give rise to a d:ifferent potential than contraction. -10- EXPERL\rENT.AL APPROACH Attention will be given to possible resolution in the foregoing areas of controversy or uncertainty. Ft\le primary questions may be used as the basis for formulation of research efforts: 1. Does the skin conductance response depend upon activity in the sweat gland alone~ or d,:Jes it (in aqdition) depend upon activity in an epidermal layer or in blood vessels. 2. Do the positive and negative components of the skin ~tential response depend upon activity iri separate areasJ e. g. sweat gland and epidermis (or blood vessel) or do ther simply represent t\vo phases of a process in a single effector organ? 3. Which compoHent, epidermal or vascular most likely accounts for the ' skin potential responses observed in a sweat gland-free area such as the nail-bed? 4. What is the biological (psychological) significance of each component? Are they qualitatively different? Do they vary in sensitivity? 5. How do separate elements in the skin, combine to :1ccount for a given conductance level or a given potential? To what 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 respon~e amplitude for differe::1ces in base level? Method Each of the above postulated mechanisms represents a target for experimental evaluation as to its actual role in the electrodermal reflex. As -11- the tenability of each of these is experimentally indicated, attention will be given to the relative magnitude The visible content of this page shows a typed document featuring text related to "EXPERIMENTAL BACKGROUND" and "Areas of Agreement" concerning the galvanic skin response. There are no photographs, handwritten annotations, or official stamps visible. The content is presented as a numbered list of observations or conclusions regarding the electrodermal reflex. There are no diagrams or visual representations of experimental procedures, equipment, or facilities, and no redacted content is present. of observed respon~e amplitude for differe::1ces in base level? Method Each of the above postulated mechanisms represents a target for experimental evaluation as to its actual role in the electrodermal reflex. As -11- the tenability of each of these is experimentally indicated, attention will be given to the relative magnitude of contribution both to baso2 le·.1el and response amplitude, and to the manner in which its contribution interacts with contribution of the other components. In each case skin conductance, skin potential, SCR and SPR will be simul:aneously observed for quantitative test of interaction effects as well as consistancy with each proposed model. Specific experiments designed to aid in the answer to each primary question are outlined below. 1. Is the sweat gland alone involved in the skin conductance response? a) Microelectrode experiments based on the isolated epid~rmal slab technique (18) will be continued in an 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-form relations of simultaneous recordings from the slab and nearby sweat glands. b) All sweat glands in a micro field will be selectively inactivated by the iontophoretic introduction of silver ion (method already established by principal investigator) and observations made Of recordings irom 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. Preliminary experiments reveal that sweat glands continue t-o secrete after this procedt.:re. Tht; effect of this treatment on conductance and on conductance response will be examined. -12- d) The avcr;:tgc sweat gland (microclcctr::ldc) response amplitude 2 and resistance level from a 0. 3 cm field will be compared with that from a simultaneously recc•rded macroscopic site by a sampling tedUli=lue. Total sweat gland connt will also be made in this delineated area. A gross electrode will tncn be applied to this 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 mil6.ria will be used to block sweat glands selectively. This mefuod, _~~involves stimulation of keratin formation ac the sweat pore by use of high currents. Affected areas will be compared with ajjacent sweating areas. f) Atropine has been shown to block all SCR The image displays a scanned document page with typed text and a few handwritten annotations. The text is primarily structured into numbered points and a section titled "Controversies Posed by Experimental Findings." There are also faint horizontal lines, possibly remnants of previous document formatting or marks from the scanning process, as well as a distinct circular mark at the top center of the page, which could be an ink blot or a stamp. A black vertical line runs along the right margin. No photographs, diagrams, forms, or official stamps are visible. There are no visible redactions or obscured content. indications of non-sweat activity. \ e) E::-..--perimental mil6.ria will be used to block sweat glands selectively. This mefuod, _~~involves stimulation of keratin formation ac the sweat pore by use of high currents. Affected areas will be compared with ajjacent sweating areas. f) Atropine has been shown to block all SCR activity but the effect is inconclusive for resolution of the present question since oth<:r effectors may also be cholinergic. Pilocarpine induces profuse sweating and may be considered to raise sweat gland ourput to a maximal level. Therefore any alteration in skin resistance after ior_tophoretic introduction of pi19carpine (30), 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 atropine. g) The sweat gland may be having an indire'?t but important effect on SCR amplitude by virtue of the induced change in corneal hydration as postulated -13- If he is correct, one should expect SCR amplitude to be just as large with a constJ.nt current system as with a cor:stant voltage system even with a relatively ''dry" electrolyte such as 0.1 N.:!.Cl in 90 per cent glyceroL If change in hydration is relatively minor the constant voltage system will result in diminished ampliLtde, owing to a significant loss of the "cons:ant'' voltage across the non-varying corneal resistor. 2. Do the positive and negative components of the SPR originate in separate sites? Because of unavoicbble electrical leaks one can always expect contamination of signals in one area by those in the adjacent area. Results of rnicroelectrode surveys will therefore be suggestive rather than definitive. Moreover, the positive and negative components, though slightly out of phase, are to a great extent fused and subject to partial. cancellation. In fact a positive wave may occur \Vithout the combined wave ever going positive (31). Resolution of the two components is understandably difficult. a) Experiments on epidermal slabs (microelectrode) previously confined to conductance measurements will be extended to potential measurements. Wave forms from the two areas will be examined for predominance of either polarity. b) The effect of Ag-''- im.ctivation of the s·weat gland on microelectrode wave forms of response from various areas will be determined. c) The application of an external load (shunt) will be used to determine whether the intenml resistance of the positive and negative geaerators are different. -14- If the two wa vcs o.rc ::!iffcrcntblly o.ttcnuatl'd when a This document page contains typed text with no visual representations of people, locations, equipment, or subjects. There are some handwritten annotations, including a bracketed phrase and a short line beneath it, as well as a horizontal line that appears to be a partial underline. The number "-6-" is present at the top center of the page, indicating a page number. There is a small circle with a dark filled center and a light ring at the top center of the page, which could be a printing artifact or a part of a stamp. Otherwise, the page is primarily text. s·weat gland on microelectrode wave forms of response from various areas will be determined. c) The application of an external load (shunt) will be used to determine whether the intenml resistance of the positive and negative geaerators are different. -14- If the two wa vcs o.rc ::!iffcrcntblly o.ttcnuatl'd when a low resistance shunt is used, this would be evidence: for different internal resistances of these t\VO components and t:tercfore for different sites. It \Vould be important to rule out temporal changes in the impedance of a single generator, as an alternative explanation. This wo:>uld be done by comparing the magnitude of any difference in the internal resistance with the ma..ximum variation in total resistance observed during d1e response. This latter can be determined by a simultaneous writeout of resistance using a. 5 mv, low frequency AC source (32). __ --.___ d) The· report by. · j that high current density differentially affects d1e positive and negative components of the SPR will be followed up by a . micro electrode study. High currents will be applied selectively to sweat glands and n