Product Design
The Effects of Cigarette Smoking on Pattern Reversal Evoked Potentials (PREPs)
Abstract
Describes the effects of cigarette smoking on pattern reversal evoked potentials [PREPs] and overviews the key components of this area of research. Details experimental design and reports human central nervous system [CNS] brainwave response is a function of nicotine delivery.
Fields
- Author
- Gullotta, Frank Paul, Ph.D. (Tobacco chemist, Philip Morris, Cologne, Germany '94)Developed and used EEG techniques to study relationship between nicotine addiction and blend properties. Worked moved off-shore in 1986 to avoid discovery.
- Shultz, C.J.
- Recipient
- Dunn, William L., Jr. (PM Smoker Psychology Principal Scientist 1970s-80s)Principal scientist at PM during the 1970s and 1980s, nicknamed the "Nicotine Kid." Supervised Victor DeNoble, Paul Mele, Carolyn Levy and others. Led "smoker psychology" programs for PM.
- Seligman, Robert B. (PM VP of R&D c. 1976-82)
Vice President of Research and Development at Philip Morris Richmond, VA 1976-1982. Reported to Senior Vice President of Operations. In 1982 transferred to tobacco technology group. Wanted to share ammonia and other tobacco technology with PM International companies.- Osdene, Thomas Stefan, Ph.D. (Director of Science and Technology, Philip Morris [1986])
Ph.D. in Organic Chemistry. Ten years of research when he started with PM in 1965. Worked in Chemical Research Division of PM 1965-66; Chemical and Biological Research Division 1966-69; Director of Research 1969-1984, also assumed independent position as Director of Research and Extramural Studies during these years; became Director of Science and Technology in 1984, reporting directly to Philip Morris USA Executive VP Mark Serrano. Involved with Center for Indoor Air Research (CIAR) 1988. Attended PM's Operation Downunder Conference in June, 1987. Retired 1993.- Charles, James L., Ph.D. (PM, R&D VP, Pharmacologist, Industry Expert)
Vice President of Research and a scientist for Philip Morris, Inc. Vice President of Research for Philip Morris, Inc. in 1986 and then again from 1992 to 1993.- Fagan, Raymond (PM Principal Scientist c. 1968-83)
Principal Scientist at Philip Morris Research Center in Richmond, Virginia, between around 1968-84. - Seligman, Robert B. (PM VP of R&D c. 1976-82)
- Hypothesis
- Inhalation ProfileAre cigarettes designed to cater to individual inhalation profiles?
- Measuring human intake
Development of scientifically valid procedures for measuring tar and nicotine levels that more accurately reflect human intake.- Nicotine transport, transfer, and uptake
Design changes which alter nicotine delivery or effect how the product causes and maintains dependence, including transfer of nicotine from tobacco to smoke, and uptake into the body.- Smoking psychology and behavior
- Neurobiology
- Measuring human intake
- Keyword
- Behavioral effects (Behavioral pharmacology)Addiction behavior, withdrawal, and measured nicotine effects
- Brain activity
- Central nervous system (CNS)
- Human testing
- Neuropharmacology (Electrophysiology)
Receptor, brain, and CNS effects (EEG, trigeminal response, etc.)- Nicotine delivery (Smoke nicotine or nicotine yield)
- Physiological effects
- Sensory response
- Smoker behavior (Human smoking behavior)
Puff parameters, daily intake, etc. - Brain activity
- Smoke Constituent
- Nicotine
- Named Organization
- Biobehavioral Research Laboratory
- Brand
- Marlboro (PM)
- Subject
- Behavioral Effects (Effects)
- CNS/Brain (Effects)
- Effects—Smoking Behavior (Effects)
- Experimental Technology (Technology)
- nicotine technology
- Receptors (Effects)
- CNS/Brain (Effects)
Document Images
PHILIP MORRIS INCORPORATED
CONFED3-NTIAL ts
INTER-OFFICE C~ORRESPONDENCE
RICHMOND, YIIRGINIA
To:
Fror:
Dr. W. L. Dunn
F. P. Gulliotta and C. J. Shuiltz
Date:
`1
r: 6-;E-tiC3®UC i'S
February 4, 1981
Subject: . Th,e Effects of Ci arette Smoking on Pattern Reversal Evoked
Potentials (PREPs3
Since its inception, one of the goals of the neuropsychology
laboratory has been to identify responses of the human brain
which change in a predi~ctable and reliable manner as a function
of cigarette smoking. Over the 1!ast several months we have
been conducting research on what appears to be such a response.
This memo describes the first study we have completed on the
effects of cigarette smoking on pattern reversal evoked'~ pot-
entials (PREPs).
In the 1960s David Hubel and Torsten Wiesel demonstrated that
the visual system optimally responded to patterns and edges
which moved across the visual field in very specific orientatiions.
The system responded considerably less well to diffuse illumin-
ation. Based upon this work, subsequent research showed that
very relliable visual evoked potentiials could be obtained by
employing shifting (reversing) checkerboard patterns. Their
reproducibility was such that neurologists began testing
their sensitivities to various pathophysiologies of the central
nervolus system (CNS):. The response is currently used to diagnose
a number of pathologic processes in the CNS, i~ncluding: optic
neuritis, compressive lesions and multiple sclerosis..
Despite the great popularity of the PREP in cliinical medicine,
there is a paucity of basic research on the topic. In particular,
there have been very few reports of pharmacologic influences
on the response. The data presented here strongly suggests the
modifiiabiliity of the response by nicotine and nicotine d'epriv-
ation.
The PREP. has three principal components or peaks (see Figure 1).
The fi~rst negative peak (N1) has a latency of. approximately 70
msec,' and its neural generators are postulated to be located,
in striate cortex. The first positive peak (P1) occurs at
approximately 100 msec, and it is believed to be.generated in
occipital cortex. The second negative peak (N2), which is also
thought to be of occipital origiini, has a latency of about 1510
msec.
Dr, V. .L..' Dunn
Februa;ry._4 1981 OS
;. _. L 4 r1!12 V
PR©DUCTS
Altho~ugh the N,2 peak is quite variable within and between
subjiects, both the N, and P1 components are characterized by
a high degree of inter and intra subject reliability. There-
fore, we have chosen to restrict our discussion to the data
analyzed on these two earlier peaks. We believe that the nature
of the changes reported herein, are quite robust and will endure
in the light of future research.
Ten, male R&D employees were used to assess the effects of
cigarette smoking on PREP's. They were asked to abstain,
overnight, from cilgarette smoking, and then were required to
smoke, on seplarate occasions, cigarettes delivering either
:14 mg (low) or 1.34 mg (high) nicotine, or to sham smoke
(no nicotine) an unlit cigarette. Both cigarettes which were
smoked we.re Marlboro blends, with very similar tar, CO and RTD
values. PREPs were recorded, via a vertex-positive electrode,
both before (pre) and after (post) smoking.
Figure 2 ill!ustrates the effects of smoking on the amplitude
of N1 component. As figure 2 indicates, pre-post values in
the siio-(no nicotine) smoking condition were nearly identical.
In the low nicotine condition there was a post-smoking amplitude
decrease, but the effect was not stati'stically significant. In
the high nicotine condition, the post-smoking amplitude de-
cliined by 0.92 uv. This effect was statistically significant
(t = 2.43 df = 9, p < .05).
Figure 3 illustrates the effects of smoking on Py latency.
In the sham smoking (no: nicotiine) cond'ition, there was a slight,
but non signiifilcant post-smoking latency increase. In the low
nicotine condition, there was a post-smoking decrease-iniP1
latency, but this effect also failedto reach statistical
significance. In ni.ne out of ten subjects there was a post-
smoking decrease in P1 latency in the high nicotine cond~ition.
The average latency decrease, in this case, was 2.79 msec, and
this effect was statistically significant (t = 3.08, df = 9,
E < .0~5).
One additional finding is worthy of note. In almost every
subject, smoke deprivation apparently ind'uced abnormalities
in the shape of the PREP waveform. It can be seen, in Figure 1,
that the typical PREP is si,nusoidal in shape, with two distinct
negative peaks at approximately 70 (N1) and 150 (N'z) msec.,
respectively, and a very prominent positive peak (P1) at
approximately 100 msec. In Figure 4 are PREPs from three
individuals followiing overnight deprivation (pre) and following
the smoking of a high nicotin~e cigarette (poist). In the first
examp,le, the entire pire-smoking, waveform is grossly distorted.
In examples 2 and 3, there is an unexplained additional comp-
onent occurring, at 125 msec. Finally, in all of the pre-smoking
records, the N2 component is.not well defined. Post-smoking,
~./
ATTORNEY Dr. W. L. Dunn -3- 4e~~RPIQ;118
however, each waveform assumes a more or less sinusoidal and
normal appearance.
Our data are interesting in several respects. First, using
noninvasive techniques, we have presented evidence which suggests
where and how cigarette smokinig is influencing the human brain
(i.e., the N1 and Pi PREP components are believed to be gener-
ated in striate and occipital cortex respectively, and were
affected differentially). Second, we have demonstrated a
human CNS response which varies systematically as a function
of nicotine delivery. Finalliy, we have shown how a system
which participates in the processing of visual iinformation is
affected by cigarette smokiing and smoke depriva~tion.
Research currently under way is aimed'. at determiining how the'PREP
responds to suistained visual stimulation (habituation study)
and how the response is influenced by other classes of centrally'
active compounds (caffeine study).
fiw
Enclosure
cc: Dr.
Dr.
Mr.
Dr. R.
T.
J.
R. Seligman
Osdene
Charles
Fagan
Behavioral Research Laboratory
ATTORN...r.y
~~ .
The PREP
FIGURE 1. Representative PREP recorded from vertex - positive
lead. Me.g!ative up.
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SMOKING CONDITION (NICOTINE)
FIGURE 2.. Figure.illustrates effect of Smoking on N1 ampljtude. The effeGt is
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SMOKING CONDITION (NICOTINE) .
FIGURE 3. Figure.'illustrates effects o€ smoking on PI latenqy,, The effect is statisticcL
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FIGURE 4.8 PREP's ff'rnm three subjects following overnight smoke deprivation
.. (pre) and.following, the smoking of a high nicotine cigarette
(post)
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FIGURE 3. Figure illustrates effects of smok.ing on P1 latency._ The effect is statistic-
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FIGURE 2..
Fi aure i l 1 ustrate Sef9lc~aft smo'ki'nlg ron=N~Im~pf i tu~ N"fifie~ ef'~~cti'?s
