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Master's Theses Graduate College
8-1972
Spectral Analysis of Olfactory System Electrical Activity: Effects of Ketamine and Sodium Pentobarbital
John Ludwig Orr
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Recommended Citation Orr, John Ludwig, "Spectral Analysis of Olfactory System Electrical Activity: Effects of Ketamine and Sodium Pentobarbital" (1972). Master's Theses. 2815. https://scholarworks.wmich.edu/masters_theses/2815
This Masters Thesis-Open Access is brought to you for free and open access by the Graduate College at ScholarWorks at WMU. It has been accepted for inclusion in Master's Theses by an authorized administrator of ScholarWorks at WMU. For more information, please contact [email protected]. SPECTRAL ANALYSIS OF OLFACTORY SYSTEM ELECTRICAL ACTIVITY EFFECTS OF KETAMINE AND SODIUM PENTOBARBITAL
by
John Ludwig Orr
A Thesis Submitted to the Faculty of the Graduate College in partial fulfillment of the Degree of Master of Arts
Western Michigan University Kalamazoo, Michigan August 1972
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ACKNOWLEDGEMENTS
In the course of preparing this thesis I have benefited from
advice and discussions with Drs. Fred Gault, Ronald Hutchinson and
Arthur Snapper- My thanks go to them and especially the staff at
the Western Michigan University Computer Center who gave patiently
of their time. Of course, I assume the sole responsibility for what
is written here.
John Ludwig Orr
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. INFORMATION TO USERS
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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. MASTERS THESIS M-4247
ORR, John Ludwig SPECTRAL ANALYSIS OF OLFACTORY SYSTEM ELECTRICAL ACTIVITY: EFFECTS OF KETAMINE AND SODIUM PENTOBARBITAL.
Western Michigan University, M.A., 1972 Physiology
University Microfilms, A XEROX Company, Ann Arbor, Michigan
THIS DISSERTATION HAS BEEN MICROFILMED EXACTLY AS RECEIVED.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. PLEASE NOTE:
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University Microfilms, A Xerox Education Company
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. TABLE OF CONTENTS
CHAPTER PAGE
I INTRODUCTION...... 1
The Purpose...... 1
Advantages of Digital Analysis ...... 2
Window Closing ...... 3
Stationarity ...... 3
Stability and Fidelity ...... 4
II METHODS AND MATERIALS ...... 5
Electrodes ...... 5
Implantation ...... 5
Recording...... 6
Ketamine...... 7
Barbiturate...... 7
Digital Spectral Analysis...... 7
III RESULTS...... 10
IV DISCUSSION...... 40
V REFERENCES...... 47
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. INTRODUCTION
Time domain displays of the electrical activity of the olfactory
system are similar across a wide range of species (Adrian, 1950).
The analysis of component frequencies in olfactory electrical activity
by analog methods led Hughes and Hendrix (1967) to propose that the
frequency components encode information concerning the nature of an
olfactory stimulus. The purpose of this study was to implement
digital frequency analysis techniques on a large digital computer
to obtain the frequency components in olfactory system electrical
activity and evaluate a potentially useful class of anesthetics for
use in recording electrical activity in acute preparations.
Olfactory system electrical activity is intimately related to the
activity of the midbrain reticular formation and is very sensitive to
the effects of anesthetics. Electrical stimulation of the midbrain
reticular formation increases the amplitude of olfactory spindle
bursts (Pagano, 1966), and barbiturates, which depress the reticular
system (Sharpless, 1970) , reduce the frequency of olfactory spindle
bursts (Hemandez-Peon, Lavin, Alcocer-Cuaron, & Marcelin, 1960;
Gault & Coustan, 1965). Ether, an anesthetic frequently used in
setting up acute preparations, disrupts the electrical activity of
the olfactory bulb for up to six hours (Gault & Coustan, 1965). Thus
for olfactory research with acute preparations, an anesthetic which
did not depress the reticular system might prove useful.
1
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2
"Ketamine has a stronger depressant effect on the diffuse
thalamic projection system than on the midbrain reticular formation"
(Miyasaka & Domino, 1968, p. 570). This conclusion, based on time
domain displays, suggested that Ketamine would be a useful anesthetic
for electrical recording in acute preparations- "Disassociative
anesthesia" is the term introduced (Domino, Chodoff, & Corssen, 1965)
to describe the state induced by Ketamine.
To evaluate Ketamine as an anesthetic for olfactory acute
preparations, rats with chronically implanted olfactory system
electrodes were used. This chronic preparation allows the recording
of electrical activity before and after drug administration without
the confounding effects of other drugs or surgical trauma. Sodium
Pentobarbital, a barbiturate, was included in the evaluation for
comparison.
The present research is closely related to that of Pagano (1966).
Pagano's measure of olfactory system electrical activity was the
integrated output of a bandpass filter centered at 40 Hz. The power
spectrum, the dependent variable in the present research, may be
considered the distribution of the integrated electrical activity
by frequency.
The analysis of electrical activity into components may be
performed with either analog or digital apparatus. At the present
time, analog methods do not have all the advantages of digital methods
implemented on a large digital computer. For example, multivariate
spectra have been computed by digital methods and plots of phase and
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. coherence spectra used to describe the relationships between time
series recorded from different electrodes (Walter & Adey, 1965).
A major advantage of digital analysis is that the analysis bandwidth
may be easily varied. This leads to the routine practice of
conducting the analysis of a given time series at several bandwidths.
Spectra obtained with the different bandwidths are then compared to
judge the quality of the digital analysis for a given number of data
points. This process is called window closing and allows after the
fact selection of the most suitable bandwidth for a given record
(Jenkins & Watts, 1968, pp. 280-281).
Spectral analysis is the term used to refer to adaptations of
Fourier analysis to the analysis of nondeterminate stationary time
series. Digital cross-spectral analysis was first applied to the
electrical activity of the brain in studies of learning by Adey,
Walter, and Hendrix (1961). Since that time a number of reports
involving spectral analysis of brain electrical activity have
appeared, including Walter (1963), Adey (1965), Elazar and Adey (1967)
and Adey (1969).
Stationarity is a concept important to the evaluation of the
appropriateness of spectral analysis because a stationary time series
is completely described by the lower moments of its probability
distribution (Jenkins & Watts, 1968, p. 3). The lower moments
involved in the description of a stationary time series are the mean,
standard deviation, autocovariance, and the power spectrum, which is
the Fourier transform of the autocovariance (Jenkins & Watts, 1968, p.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. A stationary time series is one which exists in a state of statistical
equilibrium with no trends (Jenkins & Watts, 1968, p. 4); in other
words, the series is independent of clock time (Jenkins & Watts, 1968,
p. 147). Even in cases where the empirical time series is non-
stationary, spectral methods for stationary series are an appropriate
starting point because nonstationarity in the mean will appear as a
low frequency peak in the spectrum (Jenkins & Watts, 1968, p. 8).
A useful test for self-stationarity is the examination of more
than one spectra obtained in a given experimental condition. If the
variability is small, the process generating the spectra is self-
stationary (Bendat & Piersol, 1966).
Spectral analysis has the property that the product of the
bandwidth of the digital filters and the variance of the spectrum
obtained is a constant (Jenkins & Watts, 1968, p. 257). This means
that to obtain a high degree of spectral stability for a given length
of record, one should use wide bandwidth digital filters. Fidelity,
however, depends upon having digital filters on the same order of
magnitude of bandwidth as the narrowest detail of interest in the
spectrum (Jenkins & Watts, 1968, p. 279). The challenge of conducting
an analysis which is stable enough to demonstrate spectral changes
between experimental conditions and yet allows the display of as much
spectral detail as possible is met by window closing.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. METHODS AND MATERIALS
Four male Sprague-Dawley albino rats from the Upjohn Company
colony were implanted with coaxial bipolar electrodes under Sodium
Pentobarbital anesthesia in clean but not aseptic conditions
Atropine sulfate was administered to reduce respiratory system
secretions. The electrodes were constructed from 26 gauge #303
stainless steel hypodermic tubing with 0.0063 inch diameter #303
stainless steel wire passing through the tubing and extending 0.5
to 1.0 mm. for the olfactory bulb electrodes and 2.0 to 3.0 mm. for
the prepyriform electrodes. The electrodes were insulated with
Formvar and the recording surfaces were exposed by scraping clear
0.5 mm. of the barrel and 0.5 mm. of the tip, leaving insulation
between.
Olfactory bulb electrodes were inplanted under visual control
by observation of skull surface landmarks and subsequent histological
examination confirmed that all olfactory bulb electrodes were
appropriately placed. Three subjects were also implanted with
concentric bipolar electrodes straddling the ipsilateral prepyriform
cortex dipole generator layer by using the method of Freeman (1960).
In this procedure, single pulses from a Grass S-4 stimulator and
SIU-4 isolation unit were delivered across the olfactory bulb
electrode. The prepyriform electrode surfaces were connected for
monopolar recording from each surface by using Tektronix 122 pre
amplifiers, with the evoked response from each surface displayed
5
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. on a channel of a Tektronix 564B storage oscilloscope- As the dipole
generator layer is approached and crossed, the evoked potential
recorded from the prepyriform electrode tip flattens and then inverts
to form a mirror image of the evoked potential recorded from the
barrel. This gives the investigator positive evidence that he has
one recording surface on each side of the generator layer (Freeman,
1960). The stereotaxic target for the beginning of stimulation was
as follows: anterior, 9.0 mm.; lateral, 4.5 mm.; and depth, 0-0 mm.
(Pellegrino & Cushman, 1967). Various types of miniature plugs were
used for connecting the electrodes to the recording equipment and
were attached to the skull with dental acrylic. Bicillin was
administered post-operatively to minimize the likelihood of infection.
During recording sessions, which began at least a week following
surgery, the subject was in a 15 cm. by 15 cm. by 15 cm. Plexiglas
box with a grid floor. The box was located on a shelf in a
refrigerator cabinet which was equipped with a fan for ventilation.
Connections were made from the rat to a Grass Model 7 polygraph
equipped with capacitor coupled preamplifiers and interfaced with
a Sanborn model 2000 frequency modulated tape recorder. The
polygraph provided an ink written time domain display of the lower
75 Hz. of the data stored on magnetic tape. The recording system
was calibrated with a digital voltmeter before each session. Once
amplifier gain settings were determined for a given session, they
were not changed; therefore the spectra obtained are relative but
not absolute. Recording began after exploratory behavior by the
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. subject had decreased to a low level. Baseline recording was carried
out until several sections of record with steady olfactory bulb slow
wave activity were obtained. Ketamine (Vetalar from the Parke-Davis
Co.) was administered by intraperitoneal injection in a dose of
50 mg/kg. At least five days intervened before Sodium Pentobarbital
(Fort Dodge Laboratories) was administered by intraperitoneal
injection in a dose of 60 mg/kg. Electrical activity from the
olfactory bulb electrode was simultaneously displayed on two channels
of the polygraph. One channel was set to display bulb slow wave
activity with the polygraph filters set at 0.15 and 3.0 Hz. The
second bulb channel was used to display fast activity with filter
settings of 10 and 75 Hz. for chart write-out and 10 and 500 Hz. for
the tape recorder. Prepyriform activity was displayed on another
channel using the same filter settings as for bulb fast activity.
Bipolar recording was done between the tip and barrel of the
electrodes.
The abstracting of approximately six second sections of
electrical activity for computer analysis was accomplished by
selection of records which showed steady olfactory bulb slow wave
activity. Once segments were selected for analysis, they were
saitpled and stored on computer compatible magnetic tape by a
Massey-Dickenson data acquisition system.
Spectra are analyzed to a maximum frequency of one-half the
rate of sampling of the analog signal. In order to avoid "aliasing"
(interference from harmonics), it is necessary to have all significant
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. spectral power within the range analyzed (Blackman & Tukey, 1959;
Walter, 1963; Jenkins & Watts, 1968, pp. 51-53). In this study, a
preliminary sampling rate of 300 Hz. was selected on the basis of
acute experiments in which the spectrum was analyzed to 350 Hz.
After the effect of Ketamine was observed, most Ketamine records
were resampled with a 420 Hz. sampling rate. The price one has to
pay for a higher sampling rate is that less real time is analyzed
for a given number of data points. Thus there is good reason for
not using a higher rate of sampling than necessary.
Each digital magnetic tape contained a number of individual
data records, and before the analysis began, certain sorting
operations were performed. As the lon£ file from the magnetic
tape was converted into one-record files for data analysis, the
number of "greater than full scale" codes, the number of blank
characters, and the identifiers which were inserted manually at
the time of analog to digital conversion were typed out on a teletype.
This allowed monitoring of all parts of the digital system. For
example, the occurrence of "blanks" on the tape indicated dirty tape
heads and that cleaning and resampling were necessary.
Spectral analysis was carried out in the time sharing mode of
the PDP-10 computer, losing a locally modified version of program
BMDX-92 "Time Series Spectral Estimation" from the Health Sciences
Computing Facility (University of California, 1969). The same
2048 data points in each record were analyzed into 8, 16, 32, and
64 frequency bands for window closing. This particular program does
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 9
not compute the autocovariances as an intermediate step in computing
the power spectrum. Since the covariances are not available, it was
concluded that cross-spectral analysis would not be prudent (Jenkins
& Watts, 1968, p. 396). With a sampling rate of 300 Hz., the digital
filter bandwidth for 32 bands was 4.7 Hz., and for a 420 Hz. sampling
rate, the filter bandwidth was 6.7 Hz. For a record of 2048 data
points, resolving the spectrum into 8, 16, 32, or 64 bands results
in 256, 128, 64, or 32 theoretical degrees of freedom respectively
for the spectral estimate (University of California, 1969). Instead
of accepting the theoretical degrees of freedom, window closing was
performed. Since the ends of this study were best served by trading
off high fidelity for high stability, the window closing procedure
led to the selection of the 32 band estimates for comparison.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. RESULTS
Differential spectral changes were observed following the
administration of Ketamine and Sodium Pentobarbital. Ketamine
injection was followed in three subjects at all electrode sites by
a dramatic increase in power above 100 Hz. The high frequency peaks
following Ketamine are centered at the same frequency within subjects
and at different frequencies across subjects. One subject showed no
change in the spectra obtained following Ketamine injection. It is
possible that this lack of effect was due to an ineffective intra
peritoneal injection. Since Ketamine does not decrease muscle tone
and the eyes remain open, it is not possible to determine by visual
observation if the subject is anesthetized. Spectra obtained following
Sodium Pentobarbital injection show a reduction of spectral power at
frequencies below 100 Hz., with occasional increases at around 10 Hz.
Table 1 displays the changes observed following drug
administration. Spectral overlays of three spectra obtained before
and three spectra obtained 5 to 20 minutes after drug administration
are presented for each subject, drug, and electrode site in Figures
1-14 and discussed individually in the figure captions.
10
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. TABLE 1
SUMMARY OF SPECTRAL COMPARISONS
KETAMINE:
Subject Site Page Frequency Range in Hertz
<20 20-100 >100
PO B 21 - - +
B B 32 + +
P 33 - + +
J31 B 28 - + f
P 29 + +
A3 B 24 - - -
P 25 - --
SODIUM PENTOBARBITAL Subject Site Page Frequency Range in Hertz
<20 20-100 >100
PO B 20 - + -
BB 30 + -
P 21 + 4 -
J31 B 26 - + -
P 27 - - -
A3 B 22 - 4- -
P 23 + + -
Note.— B=olfactory bulb; P=prepyriform cortex; +=increase following drug administration; 4=decrease following drug adminis tration
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 1:
Subject PO, olfactory bulb spectra before (dashed lines)
and after Sodium Pentobarbital (solid lines). (The ordinate on all
the spectra is in relative units of natural logarithm of power
(microvolts/frequency band across an assumed one-ohm load).)
Post-drug spectral power was reduced between the 53.8 Hz. and the
80.6 Hz. bands and increased in the 20.2 Hz. to 33.6 Hz. bands.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 13
Figure 1
-&0-i
k x q 33*6 67.2 1008 1344 168.0 2QL6 Hz.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 2:
Subject PO, olfactory bulb spectra before (dashed lines)
and after Ketamine (solid lines). A large spectral increase oc
curred in these records between the 134.4 Hz. and the 201.6 Hz.
frequency bands.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. without prohibited reproduction Further owner. copyright the of permission with Reproduced
-In P &54 0 2 0S 34 MA 2014 A IM 1344 10OS 12 < Figure 2 Figure z. H V ^ - V V 15 Figure 3:
Subject A3, olfactory bulb spectra before (dashed lines)
and after Sodium Pentobarbital (solid lines). The decrease
between 23.4 Hz. and 51.6 Hz. bands is associated with an
increase between the 9.4 Hz. and 18.8 Hz. bands and is similar
to the response observed for subject PO in Fig. 1.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 17
Figure 3
5jO= 53-=
6 3 =
7.0= & c7.5=: 7 8 0 =
8 5 = 9 0 =
* 5 =
1 Q O I I I I I | I I I I | I I I I I I I I I I I I I I I I I I I I I | 0 2 3 .4 46.9 7 0 3 9 8 8 11Z2 14016 Hz.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 4:
Subject A3, prepyriform cortex spectra before (dashed
lines) and after Sodium Pentobarbital (solid lines). The decrease
between the 46.9 Hz. and 70.3 Hz. bands is associated with an
increase in the range from the 0 Hz. to the 18.8 Hz. band. This
change occurred at a higher frequency range than did the change
observed at the olfactory bulb electrode shown in Fig. 3.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 19
Figure 4
Y Y Km > AV \
t+*7 * i ! . / /* .W!
4 6 .9 7 0 3 9 1 8 117.2 1 4 0 6 Hz.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 5:
Subject A3, olfactory bulb spectra before (dashed lines)
and after Ketamine (solid lines). It was stated in the text and
Table 1 that Ketamine did not have an effect on the electrical
activity of this subject and an ineffective intraperitoneal
injection was suggested- This implies that at the time of
recording, the drug dose was much smaller than for the other
subjects. In light of the lower effective dose for this subject,
the increase in the range of the 168 Hz- to 188.1 Hz. bands is
suggestive of a change in the high frequency range. The large
peak near 60.1 Hz. is a 60 Hz. artifact.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 21
Figure 5
5 0 —,
U
7J0-
&S-:
100 67.2 lOOul 1344 168J0 20L6 H z.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 6:
Subject A3, prepyriform cortex spectra before (dashed m lines) and after Ketamine (solid lines). No obvious change is
observed for this electrode site.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 23
Figure 6
7XH\
3>5-j
«OH
l Q O d 6Z2 KKX8 134.4 1680 20i6 Hz.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 7:
Subject J31, olfactory bulb spectra before (dashed lines)
and after Sodium Pentobarbital (solid lines). A broad decrease
is observed from 46.9 Hz. to the 84.4 Hz. band but there is no
low frequency increase as was seen in Fig. 1 and Fig. 3.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 25
Figure 7
50—,
5 5 ^
6 0 ^
70-1
90-1
O 703 117.8 140L6 Hz.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 8:
Subject J31, prepyriform cortex spectra before (dashed
lines) and after Sodium Pentobarbital (solid lines). A variable
increase is suggested between the 4.7 Hz. and 14.1 Hz. bands but
with only two records available after drug administration, this
is not conclusive.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 27
Figure 8
: * * 83-
93-
O 46.9 703 117.2 Hz.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 9:
Subject J31, olfactory bulb spectra before (dashed lines)
and after Ketamine (solid lines)- The major feature of this
comparison is the peak-from 121 Hz. on up. It is possible that
the 75 Hz. to 98.4 Hz. peak is an aliasing artifact. The center
frequency of the peak at 131.3 Hz. is the same as observed
at the prepyriform cortex electrode site shown in Fig. 10.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 29
Figure 9
\v
7 0 3 117.2 1406 Hz.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 10:
Subject J31, prepyriform cortex spectra before (dashed
lines) and after Ketamine (solid lines). The peak center at
131.3 Hz. is the same as for the olfactory bulb site shown in
Fig. 9.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 31
Figure 10
i a o 0 46.9 703 93L8 11Z2 1406 H z.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 11:
Subject B, olfactory bulb spectra before (dashed lines)
and after Sodium Pentobarbital (solid lines). The spectral
diminution between 65.6 Hz. and 75 Hz. is associated with an
increase from 4.7 Hz. to 13.4 Hz., similar to the changes seen
in Fig. 1 and Fig. 3.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 33
Figure 11
5 0 - n
*5-E
60-=
05-^
Z O =
Z 5 - =
8 0 = 8 0 =
9 0 =
*5-=
lO O -1 | | r -|~ r | i i i i | i i i i | i i i i | i i i i | i i ! i | i ! O 13* 409 703 939 117.2 1406
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 12:
Subject B, prepyriform cortex spectra before (dashed
lines) and after Sodium Pentobarbital (solid lines). The
decrease from 51.6 Hz. to 79.7 Hz. is associated with an
increase between 4.7 Hz. and 23.4 Hz., similar to Fig. 1, Fig.
and Fig. 11.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. without prohibited reproduction Further owner. copyright the of permission with Reproduced O |1 , |I 11 | IOC I .O 5 6 5^4
-In P ^ 3 6 4 o z 7. »4 4 o a 834 «o4 j 0-£ 3
3 4. 73 3 17 1403 1173 933 703 46.9 234 O ,1 II 1 1 1 1 I 1 11 1 | i 1 1 I I 1 1I I I I I Figure 12 Figure Hz. 35 Figure 13:
Subject B , olfactory bulb spectra before (dashed lines)
and after Ketamine (solid lines). The major peak centered at
134.4 Hz. and the minor peak between 80.6 Hz. and 100.8 Hz.
correspond closely to the changes observed for the prepyriform
cortex electrode in Fig. 14.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 13
& ° - n 5.Si
e o S
& 5 - =
7 j O i & c 7 j i I 80-=
9 0 l=
M i
10.0- I'1111| I1 I M | I I I I | I I I I | I | | | | | | | | | O 316 67.2 KXXS 1364 1680 20L6 Hz.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Fi glare 14:
Subject B, prepyriform cortex spectra before (dashed
lines) and after Ketamine (solid lines). The spectra obtained
are very similar to those obtained from the olfactory bulb site.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 14
5 3 - :
d X K 64-= h WK / P T l tl 0 . /JR\»
e 7 5 - = w r t a A-- T = l / m J/X x a o - E r hi \ >-♦-] J * . / \k'\ f\ \ i 1 \ » * * \w s. ,; * \\ ' * X \ ’/ l «. ‘ * 3 ./ \A\K
l O J O ^ 1 1 I 1 | 1 1 [" n r'i i T T lT"| I I I I I | rn i | i i 3 U 1 3 M I6k0 2016 Hx.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. DISCUSSION
The application of digital spectral analysis to the electrical
activity of the olfactory system of rats revealed differential
changes following drug administration. The two drugs, Ketamine and
Sodium Pentobarbital, are different in chemical class and are described
as producing dissimilar anesthetic states in man (Domino, Chodoff, &
Corssen, 1965).
The occasional increases in power around 10 Hz. following
barbiturate administration are consistent with the report of
Hem^ndez-PecJn et al. (1960) . The decrease below 100 Hz. would
be predicted (Pagano, 1966) if barbiturate administration was
followed by more shallow respiration by the subject. Recordings
of olfactory bulb slow wave activity, a known correlate of nasal
air flow (Gault & Leaton, 1963; Gault & Coustan, 1965), support
this interpretation. Figure 15 includes a section of bulb slow
wave activity obtained before barbiturate administration and a
section following administration. The post-barbiturate slow wave
record indicates that respiration is more shallow than during the
control period. Air flow cannot account for the entire barbiturate
effect, however; air flow changes are correlated with amplitude
changes, not waveform changes as are seen in the bulb fast activity
in Figure 15. Since the reticular formation is depressed by
barbiturates (Sharpless, 1970), perhaps reticular system depression
is responsible for the waveform changes. If waveform changes as
40
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 15:
Subject J31, oscillographic displays before and after
Sodium Pentobarbital administration. BSW is slow wave activity
recorded from the same electrode as BULB (olfactory bulb). PPYR
indicates the prepyriform cortex channel.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 42
Figure 15
1 s t e PRE
J 5 0 v vf i e m bsw ~Y yV ^v/'v^ /v /u ;V \A \. * y
J tb m 4bhi B U L B
I7Sjnafcm P P Y R
POST
JsOvvfam B S W
I* -— PPYR ^
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 43
are seen for the fast activity in Figure 15 were observed in a system
in forced vibration, the change would be described as an increase in
the damping factor of the system.
Air flow arguments do not hold for the case of high frequency
power increases following Ketamine administration; such changes were
not observed following manipulation of nasal air flow in acute rat
preparations initially anesthetized with Sodium Methohexital and
maintained with artifical ventilation following spinal cord
sectioning or Gallamine Triethiodide injection (Orr, Gault, & Stewart,
1971). The power increases below 100 Hz. following Ketamine injection
for some subjects are correlated with an increase in nasal air flow.
Figure 16 includes a pre-Ketamine slow wave record and a post-Ketamine
slow wave record. The slow wave records show deeper respiration
following drug administration, thus a low frequency spectral increase
is consistent with Pagano's report (1966). Since Hughes and Hendrix
(1967) have reported increases in spectral power between 100 and
150 Hz. following odor stimulation of rabbits, the possibility of
olfactory stimulation must be considered. It seems unlikely that a
long-term (at least 20 minutes) change in the olfactory environment
would be correlated with the Ketamine injection. The possibility
that Ketamine in the bloodstream is an effective olfactory stimulant
would seem difficult to rule out.
A possible direction for future research would be to manipulate
conditions of nasal air flow directly before and after drug
administration. This would be possible in acute preparations where
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 16:
Subject J31, oscillographic displays before and after
Ketamine administration. BSW is slow wave activity recorded
from the same electrode as BULB (olfactory bulb). PPYR indicates
the prepyriform cortex channel.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 45
Figure 16 1 tie. PRE X i ^ b n B S W J jrafcm BULB
I p &PPYR W POST X vwSmBSW
I w o BULB Jȣ.PPYR
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 46
nasal air flow can be manipulated independently of respiration. This
would show whether the drug was affecting the background activity or
the olfactory spindle bursts. The development of a computer program
which computed the appropriate covariances would make practical the
investigation of multivariate spectra to determine frequencies shared
between the time series arising from different electrodes.
Ketamine was found to be unsuitable as an anesthetic for
olfactory research because of the high frequency spectral power
increase but may prove useful in electropharmacologic analysis of
olfactory system function.
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