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Departments of Physiological Sciences, Exercise and Sport Sciences, University of Florida, Gainesville, Florida 32610
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
Knafelc, Marie, and Paul W. Davenport. Relationship
between resistive loads and P1
peak of respiratory-related evoked potential. J. Appl.
Physiol. 83(3): 918-926, 1997.
This study investigated the relationship between resistive-load
(
R) magnitude, the first positive peak
(P1) amplitude of the
respiratory-related evoked potential (RREP), and load-magnitude
estimation (ME). The first experiments determined the subject's
(n = 9) ME of five R magnitudes
randomly presented at the onset of an inspiration or by interrupting an
inspiration. No significant differences were found in the slopes of the
two different presentations, but the subjects estimated the interrupted
inspiratory loads to be of lesser magnitude than loads presented at the
onset of the breath. In the second series of experiments, the
subject's (n = 6) RREPs were recorded
in response to three R magnitudes. The amplitude of the
short-latency P1 peak of the
RREP significantly increased with increases in the R
magnitude. A log-log plot of the group-averaged P1 amplitudes showed a linear
relationship with R. These results were consistent with the
hypothesis that the perceptual magnitude of the respiratory load was
related to the P1 amplitude of the RREP, suggesting the physical magnitude of the load-related stimulus was correlated with the amplitude of the cortical neural activation.
first positive peak; cortical-evoked potentials; magnitude
estimation; respiratory sensation; inspiration
INTRODUCTION THE DETECTION of added inspiratory loads to breathing,
usually resistive or elastic, has been studied by using difference threshold methods (3, 8). The load-detection threshold has been shown
to be a constant fraction of the background load intrinsic to the
respiratory apparatus and the subject (26). Magnitude estimation (ME)
of inspiratory loads has been studied by using scaling methods (2, 6,
25). The studies have shown that the perceived magnitude of an
increased extrinsic load is linearly related to the load magnitude when
a log-log transformation is used (6, 18, 25). It has also been
demonstrated that human subjects can easily scale a variety of
respiratory parameters other than mechanical loads, i.e., volume,
pressure, ventilation, and frequency (2, 6, 15, 18, 25). Psychophysical
studies have thus shown that human subjects can detect the presence and type of extrinsic load and assign a perceptual scale to respiratory stimuli associated with the mechanics of ventilation. The results, however, provide little information on the afferent transduction and
neural processing mechanisms mediating load sensation.
The activation of cortical neurons by mechanical loads has been studied
by using evoked-potential techniques to investigate the neural
mechanisms mediating respiratory-load sensation. A mechanical load
(inspiratory occlusion) was applied while simultaneously recording
from the somatosensory region of the cortex in the adult human (10,
19). These investigators reported inspiratory occlusion-elicited respiratory-related evoked potential (RREP) recorded in the
somatosensory region of the cortex. The evoked potential was similar to
mechanically elicited somatosensory-evoked potentials (SEP) reported
for the hand and leg. The first peak observed in all subjects,
P1, was a positive voltage that
was suggested to be an exogenous peak because of the dipole that occurs
when a cerebral cortical column is depolarized by the arrival of
activity from a population of afferents that are activated by the
occlusion stimulus. It has also been demonstrated that this RREP can be
elicited by occlusions presented either at the onset of inspiration or
by interruption of the breath after the onset of the inspiratory effort
(near midinspiration) and is present bilaterally in the somatosensory region (19). However, inspiratory occlusions were the only mechanical load tested, and the relationship of the RREP to the perception of a
ventilatory load has not been determined.
Franzén and Offenloch (14) reported that the magnitude of the
early positive peak of the touch (finger)-elicited SEP (analogous to
the RREP P1) was correlated with
mechanical stimulus amplitude and ME of the touch. It was reasoned
that, if the RREP is a SEP, then the amplitude of the
P1 peak of the RREP should
correlate with the load magnitude and associated ME. The purpose of the present investigation was to test the hypothesis that the stimulus magnitude [resistive load ( METHODS Study 1: ME of
R) magnitude] and the
P1 amplitude of the RREP are
directly correlated. The method for eliciting the RREP was interruption
of inspiration.
R
R presented as an interruption of inspiration was similar to ME of these loads presented at the onset of inspiration.
R were sinteredbronze disks placed
in series in a Plexiglas tube (loading manifold), with stoppered ports
between the disks (Fig. 1). The loading manifold was connected by
reinforced tubing to the inspiratory port of the nonrebreathing valve.
The loading manifold was hidden from the subject's view. Mouth
pressure (Pm) was recorded from a port in the center of the valve. Pm
was sensed with a differential pressure transducer and signal
conditioner (model 12, Grass Instruments). Pm was displayed on an
oscilloscope and used for timing the load application.
Five magnitudes of inspiratory resistance (2, 5, 9, 13, and 21 cmH2O · l
1 · s)
were presented at the onset of an inspiration and after the onset of
the breath as an interruption of an inspiration. The onset-load trials
were presented for the entire inspiratory effort by manually inflating
a balloon (Hans Rudolf) that closed the balloon occluder
(Rmin) port of the loading
manifold (Fig. 1) during expiration and channeled the airflow for the
subsequent inspiration through the selected R port. The
interrupted-load trials were presented for ~500 ms with the same
loading manifold by manually inflating the occlusion balloon after the
inspiration had started, using the onset of negative Pm to indicate the
beginning of inspiration. All five load magnitudes were presented a
total of 10 times each for both onset and interrupted inspirations. The
ME of each load trial was obtained by using a handheld meter with a
modified Borg scale (4). Subjects used the single turn knob to position
a needle on a meter that corresponded to the subjective rating of the
magnitude of the resistance. The scale was anchored at both ends by
allowing the subject to experience no resistance (0%) and complete
occlusion (100%) before the experiment (a practice session). A numeric
score from the Borg scale was visible to the experimenter and the
subject. As soon as the numeric score was recorded, the needle was
returned to zero in readiness for the next scoring.
The study was divided into two experiments with five trials of each
load magnitude in each experiment for both onset and interrupted inspirations. The subjects provided an estimate of the load after the
inspiration was complete. The load magnitudes were randomized in a
complete repeated-measures design, with onset and interrupted presentations randomized in the same trial. Each inspiratory load trial
was separated by three to six uninterrupted breaths. A visual cue was
used to signal a loaded breath to ensure that the subjects would
provide an estimate of the load magnitude. The cue helped the subject
maintain attention to the task and controlled for variability related
to load detection. For each breath for which he or she was
to provide an estimation of the load, the subject was visually cued by
a light on the meter during the expiration preceding the loaded
inspiration.
Study 2: RREP
The second study evaluated the effect of different inspiratory resistance magnitudes on the RREP. Subjects. Four women and two men (average age = 24 yr) who had participated in the first study were the subjects for the second study. Protocol. The subjects were seated comfortably, semireclined in the lounge chair. A standard set of instructions was presented to the subjects to inform them of their task. The subjects wore a noseclip and breathed through a mouthpiece connected to the same nonrebreathing valve and loading apparatus as described for the first series of experiments. Surface cup electrodes were placed at the scalp positions CZ, C3, and C4 according to the International 10/20 system. CZ was the reference electrode. These are standard positions for recording cortical potentials from the somatosensory region of the cerebral cortex. The ground was attached to the left earlobe. The surface impedances were checked and adjusted until they were >3 k
. The scalp electrodes
were connected to an electroencephalograph (EEG) system (model 12, Neurodata Acquisition System, Grass Instruments, Quincy, MA). The EEG
signals were band-pass filtered (0.3 Hz-3 kHz) and amplified. EEG
activity was monitored with an oscilloscope (Tektronix 5111A). The EEG
activity, Pm, and occlusion balloon pressure were led into an on-line
signal-averaging computer system (model 1401, Cambridge Electronics
Design).
The subjects were instructed to relax all postural and facial muscles
and to breathe as normally as possible. To mask auditory cues, they
listened to music of their choice. The subjects were also asked to
close their eyes to reduce visual distractions. The subject initially
inspired through the Rmin port of
the loading manifold (Fig. 1). The balloon occluder was connected to
the opening of this port. The inspiratory load was presented as
described above for an interrupted inspiration. The balloon pressure
was used to trigger the computer for data sample collection. Each load
was separated by two to six unloaded breaths. The load was applied for
a duration of ~500 ms. Three R from the first study were used that
exceeded the detection threshold
(R1 = 2.0, R2 = 9.0, and
R3 = 21.0 cmH2O · l1 · s).
Inflation of the balloon with the no-load
(R0) port open served as the
control for acoustic or other artifacts associated with the load
application.
For each subject, ordering of the four respiratory load levels was
arranged to minimize temporal, order, and sequence effects in the
following manner. Subjects received four sets of 80 trials each, with a
rest period taken between each of the sets. Within each set of 80, load
trials were tested by using 16 blocks of five trials each, with the
same load presented within a block to minimize manifold manipulations.
Ordering of the different blocks was randomly determined, with the
restriction that each successive set of four blocks contained only one
block of each load level. Thus, over the set of 80 trials, each block
of five trials of a given load was presented four times (20 total
trials). The randomization was independently drawn for each set of 80 trials and for each subject. There were four experiments, making 80 trials of each load magnitude available for signal averaging. Each
experiment was separated by a rest period. The time required to present
all four sets was ~2 h. Including subject preparation time, the
entire study session lasted <3 h.
Data Analysis
For each load presentation, 500 ms of EEG activity, Pm, and balloon pressure were digitized at 3 kHz and stored on disk for subsequent computer-signal averaging (SIGAVG, Cambridge Electronic Design). Although the digitizing frequency was greater than the high-frequency filter (1 kHz), which could lead to aliasing, the frequency at maximum power of the RREP P1 peak was ×30 less than the high-filter frequency and ×100 less than the digitizing frequency, which would make aliasing of the P1 minor or nonexistent. Each load magnitude was averaged separately. The computer stored the individual load trials in the order of presentation. The signal-averaging program recalled from memory the first set of trials. The averaged response for an individual load magnitude, for example theR2 load, was obtained by
averaging the R2 trials for
this set. The second set was then recalled from memory, and the
R2 loads from that set were
averaged with the R2 trials
from set 1. This was repeated for
trial sets 3 and
4, for a total of 80 R2 loads available for
averaging from the four sets. The averaged signals were then stored on
computer disk. This analysis was repeated for each load magnitude and
the no-load control. There were no peaks in the control average that
corresponded to the peaks observed with the load-elicited RREP.
However, to further control for possible contamination of the RREP by
artifacts, the no-load control averaged signals were subtracted from
each R average.
The P1 peak was initially identified by analysis of the averaged EEG traces. The P1 peak is the first initially positive potential occurring within 35-60 ms of the load-related change in Pm. The point of intersection of two tangent lines on the Pm tracing was used to set the time 0 point for determination of peak latencies, as described previously (11). The P1 peak amplitude and latency were measured. The P1 peak amplitude was then measured in microvolts from the control-subtracted averaged traces. The P1 peak amplitude was correlated with the resistive-load magnitude by using a log-log transformation.
The ME, with loads presented by interruption of inspiration from the
first experiment for the Rs used in the RREP experiment for each
subject, were correlated with the
P1 amplitude for that load using a
log-log transformation. In one subject, a ME of the fifth load
application in each load block was obtained during the RREP trial. A
light was turned on to cue the subject to provide an estimate of the
load on the next inspiration. Subjective rating of the perceived
intensity of the R was provided using a modified Borg scale, as
described in study 1.
A two-way analysis of variance (ANOVA) was used to test for differences
between treatments, and one-way ANOVA was used for comparisons within
individuals between the reported ME and R, and between the
P1 peak amplitude and peak
latencies of the RREP. These results were also subject to a one-way
repeated-measures ANOVA for multiple factors. A linear regression of
the log-log plot was also performed. The level of significance was set
at P < 0.05.
Study 3: Noncephalic RREP Source Controls
To determine whether there was a change in head motion during the application of theR, a series of control experiments was performed
on eight subjects (2 females, 6 males, age 11-24 yr) with no
history of pulmonary or neurological disease. The subjects were
prepared as previously described for recording EEG activity. The
subject was again seated in the same semireclined position in the chair
with an air-filled pillow positioned under his or her head. The
subject's head was centered on the pillow by using the inion as the
head reference point. The pressure in the pillow was recorded with a
catheter connected to a differential pressure transducer. Motion of the
head was recorded by a change in the pillow pressure. A
1-cmH2O change in the pillow
pressure corresponds to 2.75-mm displacement between the head of the
subject and the chair headrest. The subject respired through a
nonrebreathing valve, as described previously. The RREP R protocol
was repeated by using three magnitudes of R
(R1 = 4.0, R2 = 12.0, and
R3 = 22.6 cmH2O · l1 · s).
The EEG activity, motion pressure, and Pm were digitized at 2 kHz and
stored on computer disk. EEG activity from
CZ-C3 and
CZ-C4
and the two pressure signals were averaged as described for the R
RREP protocol.
Another series of experiments was performed on five subjects (males,
age 21-27 yr) to record the activity from the cephalic electrodes
and electrodes placed over the dorsal surface of the neck and thoracic
spine. The subjects were prepared as described for the R RREP
experiments. Scalp electrodes were placed at
C3, CZ, and
C4. In addition, surface cup
electrodes were placed at the cervical spinal
C1
(spC1) and
C7
(spC7) sites and at the thoracic spinal T12
(spT12) site. The electrode
pairs recorded were
CZ-C3, CZ-C4,
spC1-CZ,
spC1-spC7,
and
spC7-spT12.
These signals were amplified and band-pass filtered (1 Hz-1 kHz). The
subject respired through the nonrebreathing valve with Pm recorded at
the center of the valve. One magnitude of R (17.6 cmH20 · l1 · s)
and no load were presented as interruptions of inspiration. Two trials,
each with 100 load presentations, were performed with a rest period off
the apparatus separating the trials. Each load presentation was
separated by two to five unloaded breaths. Each load trial was
separated from the next by a no-load control trial. The
electrooculogram (EOG) was recorded with surface cup electrodes placed
on the lateral edge of the left eye. EOG activity was observed throughout the recording session, and a load presentation was rejected
from the trial if eye-blink-related EOG activity was present.
The Pm, cephalic, and spinal signals were averaged for the load and no-load trials. For the two load trials, the signals from both trials were initially averaged (a total of 200 presentations available for averaging) without exclusion of electrocardiogram (ECG) artifacts and then reaveraged with ECG artifacts excluded. The three spinal signals (spC1-CZ, spC1-spC7, and spC7-spT12) were displayed and examined for the presence of ECG activity characterized by large qrs-wave-associated voltage changes in spC1-spC7 and spC7-spT12 signals for each individual presentation. For the averages with ECG excluded, the presentation was included in the average only if the initial 300 ms of the poststimulus epoch was free of large qrs-wave-associated voltage changes.
RESULTS
Progressive increases in the magnitude of R presented at the onset
of the breath were linearly related on a log-log
scale(R2 = 0.94)
to an increase in the estimated magnitude of the load by the subject
(Fig. 2). The slope of the line was 0.72. When the same resistances were presented as an interruption of the inspiration, there was again a linear log-log relationship
(R2 = 0.98)
between the R magnitude and the subjects' estimation of the load
(Fig. 2). The slope was 0.70 and not significantly different from when
the loads were presented at the onset of the breath. However, the
subjects estimated the magnitude of the midinspiratory loads as smaller
than for onset presentations (Fig. 2).
, Group mean magnitude estimation (±SE) for
resistive loads presented at onset of inspiration; 
, group mean
magnitude estimation of same resistive loads presented as interruption
of inspiration. Bars, SE.
The RREP P1 peak amplitudes
increased with the increase in the inspiratory R magnitude (Fig.
3). The
P1 peak amplitudes and their
latencies are summarized in Table 1. There
were no significant differences in the peak latencies for all load
magnitudes. The increase in RREP
P1 peak amplitudes was observed in
both electrode pairs,
CZ-C3
and
CZ-C4.
There was a linear log-log relationship (R2 = 0.99)
between the P1 amplitudes and the
R magnitude (Fig. 4). The slope of both
lines was 0.35, and there were no significant differences between
CZ-C3
and
CZ-C4
electrode pairs.
R1 = 2.0, R2 = 9.0, and
R3 = 21.0 cmH2O · l1 · s.
Averaged EEG activity for each load magnitude was control-subtracted. Arrow, first positive RREP peak
(P1).
|
|||||||||||||||||||||||||||||||||||||||||||||
R magnitude. , Group
mean 0-P1 amplitudes measured
from
CZ-C3
electrode pairs; , group mean
0-P1 amplitudes measured from
CZ-C4
electrode pairs. Bars, ± SE.
The R magnitude had a linear log-log relationship with the ME of the
resistive loads and the RREP P1
amplitudes. When the results for the two studies were combined, there
was also a log-log relationship
(R2 = 0.996)
between ME and the RREP P1
amplitudes of the same loads (Fig. 5). The
slopes were 2.20 and 2.68 for
CZ-C3
and
CZ-C4,
respectively, and were not significantly different. For the one subject
in whom this comparison could be made, the relationship between
P1 peak amplitude and ME
determined in study 2 was the same as
the P1 peak amplitude-ME
relationship using the ME results of study
1.
R. , Group mean 0-P1
amplitudes measured from
CZ-C3 electrode pairs; , group mean
0-P1 amplitudes measured from
CZ-C4 electrode pairs. Group mean magnitude estimations of same R
presented as interruption of inspiration, plotted on abscissas. Bars, ± SE.
In study 3, there was a small, normal breathing-related movement of the head, as evidenced by a motion-pressure increase and decrease in synchrony with inspiration and expiration, respectively. When an inspiratory load was applied, there was no change in the motion pressure observed in the individual load presentations (Fig. 6A). There was also no change in the averaged motion pressure for all load magnitudes (Fig. 6B).
1 · s)
as an interruption of inspiration.
Top: pressure in air-filled pillow
used to record motion of head. Change in motion pressure of 1 cmH2O corresponds to 2.75-mm
motion. Bottom: Pm. Vertical line,
onset of load that produced increased negative Pm and no change in
motion pressure. These traces are for single load presentation in
individual subject. B: averaged
response to application of R3
(22.6 cmH2O · l1 · s)
loads as interruption of inspiration for individual subject. A total of
92 R3 presentations were averaged
for this subject (same as in A).
Top: averaged
CZ-C3
activity, with P1 indicated; middle: averaged motion pressure;
bottom: averaged Pm. There was no
change in averaged motion pressure with
R3 loads. Identical motion
pressure responses were obtained for the
R1 and
R2 loads (4.0 and
12.0 cmH2O · l1 · s,
respectively; not shown).
The P1 peak of the RREP was
observed in the averaged
CZ-C3
and
CZ-C4
signals for the R (Fig. 7), with no
coincident peak found in the
spC1-CZ,
spC1-spC7,
and
spC7-spT12
signals averaged with ECG artifact excluded (Fig. 7). The averages
obtained without exclusion of ECG artifact did not alter the
P1 peak in the
CZ-C3 and
CZ-C4
RREP waveforms (Fig. 8). However, the
inclusion of ECG artifacts in the averages for the other electrode
pairs
(spC1-CZ, spC1-spC7,
and
spC7-spT12)
produced voltage peaks that were not consistent among subjects.
R (17.6 cmH2O · l1 · s)
recorded in cephalic and spinal EEG electrodes, with ECG artifacts excluded. A total of 70 load presentations were averaged.
Top 2 traces:
C3 and
C4 referenced to vertex
CZ. Third
trace: vertex referenced to electrode placed at
C1 cervical spinal position (spC1). Fourth
trace: electrode placed over cervical spinal
C7 position
(spC7) referenced to
spC1. Fifth
trace: electrode placed over thoracic spinal
T12 position
(spT12) referenced to
spC7. Electrooculogram (EOG) is
averaged response recorded with bipolar electrodes placed on lateral
border of left eye. Bottom: averaged Pm.
DISCUSSION
The results of this study demonstrate that subjects can provide a ME of
R presented at the onset of the inspiration or by interrupting
inspiration. There is also a direct correlation between the amplitude
of the P1 peak of the RREP and the
magnitude of the R. In addition, the
P1 peak of the RREP recorded with
CZ-C3 and
CZ-C4
electrode pairs is not an artifact of head motion, neck and thoracic
muscle activity, or ECG activity.
ME of R requires the subjects to provide an estimate of the sensory
magnitude of a suprathreshold load by using a numerical scale or by
cross-modality matching, i.e., the magnitude of handgrip force matched
to the perceived magnitude of the load (6, 25). Respiratory mechanical
load sensation follows the general psychophysical relationship
(Steven's Psychophysical Law), i.e., the magnitude of the sensation
and the stimulus intensity is a power function related to the stimulus
conditions and type of stimulus. The results of the present study,
using load presentations at the onset of the inspiration, are
consistent with these previous reports for R ME. ME of R
presented as interruptions of the inspiration resulted in a similar
slope, indicating that the sensitivity of the subject to the R is
unaltered by the timing of the load presentation. However, the
interrupted loads were estimated to be of smaller magnitude than the
same loads presented at the onset of the breath. It has been shown that
with increased inspiratory durations, the ME of R increased (18).
The interrupted application of R used in the present study resulted
in a reduced duration of inspiration against the load. The reduction in
the ME of interrupted load presentations due to a shorter duration of
inspiration against the load would be predicted from the report of
Killian et al. (18). The similarity in slope, however, suggests that
the sensitivity of the subject to the load is less dependent on the
duration of the stimulus. Although the ME of R using interrupted
inspiratory presentations were perceived with the same sensitivity as
the onset presentations, the systematic decrease in the perceived magnitude of the loads supports the notion that the duration of the
inspiration against the load affects the perceived magnitude of the
load (18). These results, however, provide little information on the
afferent transduction and neural processing mechanisms mediating load
sensation; yet, to correlate the ME relationship with the
P1 peak amplitude of the RREP
elicited by inspiratory interruption, it was necessary to determine the
ME relationship for interrupted load presentations.
The activation of cortical neurons by mechanical loads has been studied using evoked-potential techniques similar to those routinely used in other somatosensory systems (1, 5, 14, 20, 27). Inspiratory occlusion was applied at the onset of inspiration, while simultaneously recording from the somatosensory region of the cortex in the adult human (10). Signal averaging began from the onset of inspiration. This analysis resulted in the observation of occlusion-elicited evoked potentials, RREP, recorded in the left somatosensory region of the cortex. Four voltage peaks were reported in all subjects. The P1 peak was a positive voltage that was suggested to be due to the dipole that occurs when a cerebral cortical column was depolarized by the arrival of activity from a population of afferents that were activated by the occlusion stimulus. Revelette and Davenport (19) demonstrated that the RREP can be elicited by occlusions presented either at the onset of inspiration or with interrupted inspiration. The RREP was present bilaterally (19). The evoked potential elicited by interruption of inspiration had a shorter latency for the P1 peak, which was probably due to the more rapid onset of the stimulus.
In the present study, the methods used for presentation of the load for eliciting the RREP were identical to previous reports from this laboratory (11, 19). The various magnitudes of the loads were presented in a randomized block design to control for variations in ventilatory pattern that normally occur in subjects that might affect the RREP. The number of presentations for each load magnitude were equal for each set of trials, including the control no-load presentation that allowed for the resultant averaged signals to reflect the response to the load throughout the entire experiment. The number of load presentations available for averaging is greater than the 32 reported as a minimum for observing the RREP (19) but less than the number of stimuli commonly presented for other somatosensory systems (1, 5, 14, 20, 27).
The restriction in the number of presentations available for averaging is due to the unique constraint for recording respiratory-evoked potentials of being able to present only one load per breath and the necessity to have unloaded control breaths between loaded breaths. The upper limit for load presentation number is the amount of time a subject can tolerate respiring on the loading apparatus. In this study, each load magnitude was presented 80 times. This was found to be an acceptable compromise for reliably observing the P1 peak of the RREP, accommodating subject tolerance of the protocol, and maximizing the number of presentations for averaging. The use of the point of intersection of two tangent lines on the Pm tracing for determining the time 0 point for measurement of peak latencies (11) has allowed for a standard and consistent zero point for all subjects. The application of the load occurred with the inflation of a balloon in the breathing circuit. This balloon inflated silently; however, the subtraction of the control no-load average from the loaded average removes residual non-load-related artifacts (such as auditory and vibration effects) from the load-elicited RREP. The methods used in this study controlled for variability in ventilatory pattern, allowed for consistent measurement of latencies, maximized the number of load presentations, and minimized potential artifacts.
It is possible, however, that the recordings of the peaks of the RREP,
including P1 under investigation,
were contaminated by other non-stimulus-related artifacts. The control,
no-load averages obtained during all trials showed no peaks coincident with the P1 peak. The fact that
the P1 peak was unaltered when the
control, no-load average was subtracted for each load's averaged RREP
demonstrated that the P1 peak
observed with R was not contaminated by sound or apparatus-related
artifacts. The subjects in this study were in a semireclined position,
with the back, neck, and head fully supported. When head motion was
recorded as a change in the pressure of an air-filled pillow, there
were ventilation-related slow changes in head motion that were
synchronized to inspiration and expiration. The application of a R
by inspiratory interruption produces a sudden impediment in the normal
thoracic pattern of expansion. However, there was no additional change
in head motion observed for all load magnitudes. The absence of
load-related changes in head motion, which could cause movement of the
scalp electrodes, means that such a motion artifact did not contaminate the RREP.
Sudden interruption of inspiration by occlusion has been shown to
produce a short-latency, transient inhibition followed by a brief
facilitation of neck and intercostal muscle electromyogram (EMG)
activity (7). Interruption of inspiration with R could produce a
similar change in the neck and intercostal muscle EMG, and these
voltage changes possibly alter the
P1 peak of the RREP. The
simultaneous recording from sites on the surface of the back in the
region of the neck and thorax did not directly record the EMG signal
from neck and intercostal muscles. However, EMG activity changes in
these muscles elicited by interruption of inspiration with R would
generate voltage shifts in the averaged response if such activity were
evoked by the load. No peak coincident with the RREP
P1 peak in
CZ-C3
and
CZ-C4
was observed in the neck and thoracic electrode pairs. A reduction in
EMG activity during the P1 latency
window should, in fact, favor the observation of load-related activity
in the EEG recordings. In addition, the close electrode spacing of the
CZ-C3
and
CZ-C4
electrode pairs makes the recording of distant, noncephalic voltage
changes less likely. This is further supported by the absence of
ECG-related changes in the
CZ-C3
and CZ-C4
signals. The large amplitude components of ECG activity produced peaks
in the spinal electrodes
(spC1-spC7
and
spC7-spT12). These peaks were absent when the signals were averaged when the load
stimulus occurred during the t-p interval of the
ECG. The averages, obtained with these large voltage shifts associated with the ECG excluded, showed no peaks in
spC1-spC7
and
spC7-spT12, demonstrating the absence of R-related changes in bioelectrical activity from these regions recordable by these methods. This means
that the P1 peak of the RREP
recorded from the
CZ-C3
and CZ-C4
electrode pairs is not contaminated with ECG activity or neck and
thoracic muscle EMG activity. Thus these results suggest that the
P1 peak of the RREP recorded from
CZ-C3
and
CZ-C4
was of cephalic origin and not contaminated by sound, apparatus,
motion, ECG, or neck and thoracic muscle EMG artifacts when the
recordings were made with the back, neck and head, supported.
The RREP was elicited in the present study by inspiratory interruptions
and was present in all subjects tested. The
P1 peak was present for all R
magnitudes. The latency of the P1
peak was unchanged for all the loads. This is probably due to the use of interruptions of inspiration as the method for application of the
loads. The rate of the onset of the stimulus varies slightly with this
method, whereas the primary change is the magnitude of the R. The
relationship between evoked-potential amplitude and the stimulus
magnitude was studied by Franzén and Offenloch (14). They
demonstrated that the magnitude of the touch (finger)-elicited SEP was
correlated with the amplitude of the mechanical-touch stimulus and the
ME of the touch, i.e., increasing magnitude of touch stimulus resulted
in an increase in the amplitude of the early positive peak of the
evoked potential. Zhu and Starr (27) recorded the SEP in response to
magnetic stimulation of the gastrocnemius muscle. This stimulation
activated primarily Ia afferents by mechanical contraction of the muscle. They reported a graded increase in the SEP
early positive peak (P40)
amplitude, with increases in stimulus strength magnitude that were
directly related to the muscle mechanoreceptor activation. The early
positive peaks from these studies (14, 27) are similar to the
P1 peak of the RREP. Increasing
touch magnitude also produces an increase in single-unit afferent
activity (17, 23). The magnitude of air-puff stimulation of the
glabrous skin of the hand has been reported to be directly related to
the ME of the stimulus magnitude (16). In that study, the authors
recorded the afferent multiunit activity in their human subjects. The
intensity of the stimulus was directly related to the duration of the
afferent activity, the number of impulses, and (with a reduced slope)
the frequency of discharge of the afferents. This demonstrates that the
ME of a tactile stimulus is related to the spatial and temporal
summation of the afferent activity elicited by the stimulation. Strobel
and Daubenspeck (21) reported a similar increase in the early positive
peak of the evoked potential elicited with increases in negative Pm
stimulation. In the present study, the amplitude of the
P1 peak of the RREP correlated
with the R magnitude. In addition, the magnitude of the R
correlated with the ME of the load. If this peak is similar to the
early positive peak of the SEP recorded with touch stimulation, then the amplitude of the P1 peak is a
result of the spatial and temporal summation of afferent activity
elicited by inspiring against a R. These results suggest that this
peak is a neural marker of the afferent activation of the cortical
region from which the electrodes are recording. It is, therefore, not
surprising that ME increases with increasing
P1 amplitude because this neural measure reflects the magnitude of the R the subject is estimating.
Animal studies of the neural mechanisms mediating respiratory
sensations are limited. Dogs with a tracheal stoma were behaviorally conditioned to signal the detection of an inspiratory R and
occlusions (9). The R detection threshold and Weber fraction were
found to be similar to those in humans. The application of the loads through the tracheal stoma of the dogs excluded afferent systems in the
mouth, nose, pharynx, larynx, and upper trachea from mediating this
sensation. The remaining afferents would be lung, vagal, and
respiratory muscle mechanoreceptors. The breathing pattern, as measured
by tidal volume, inspiratory duration, expiratory duration, breathing
frequency, minute ventilation, and expired PCO2, was not altered by
near-threshold, detected loads. This would make it unlikely that vagal
afferents or chemoreceptors were mediating this load detection. Phrenic
and intercostal muscle afferents have been demonstrated to activate
neurons in the somatosensory region of the cat cerebral cortex (12,
13). Specific mechanical stimulation of intercostal mechanoreceptors
elicits a short-latency activation of cat somatosensory cortical
neurons (12). These animal studies have demonstrated that the neural
substrate exists in the respiratory pump muscles for the hypothesized
respiratory muscle afferent mediation of mechanical load sensation. The
afferent pathways, cortical distribution, and neural mechanisms for
respiratory sensation in normal humans, however, remain speculative.
In summary, the results of this study have demonstrated that the amplitude of the P1 peak of the RREP is directly related to the magnitude of the stimulus and the subject's estimation of that magnitude. The afferents and neural pathways mediating the RREP are unknown. Respiratory muscle afferents have transduction properties and cortical projection pathways consistent with their hypothesized role in respiratory-load sensation. If this respiratory-related cortical activity is similar to evoked potentials for other sensory systems, then the early P1 potential would represent the arrival of the sensory signal in the somatosensory region of the cerebral cortex, similar to the primary evoked potential found with cortical surface recordings in the cat (12, 13). The correlation of the RREP (as a reflection of cerebral cortical activity) with the magnitude of the respiratory load and perceptual magnitude suggests that conscious humans use cerebral cortical sensory and motor systems as one response mechanism to respiratory loads.
ACKNOWLEDGEMENTS
Portions of this study were supported by a contract from the US Navy and National Heart, Lung, and Blood Institute Grant HL-48792.
FOOTNOTES
Address for reprint requests: P. W. Davenport, Dept. of Physiological Sciences, Box 100144, JHMHC, Univ. of Florida, Gainesville, FL 32610 (E-mail: PWD{at}VETMED3.VETMED.UFL.EDU).
Received 18 October 1996; accepted in final form 9 May 1997.
REFERENCES
| 1. | Allison, T., G. McCarthy, M. Luby, A. Puce, and D. D. Spencer. Localization of functions; regions of human mesial cortex by somatosensory evoked potential recording and by cortical stimulation. Electroencephalogr. Clin. Neurophysiol. 100: 126-140, 1996[Medline]. |
| 2. | Bakers, J. H. C. M., and S. M. Tenney. The perception of some sensations associated with breathing. Respir. Physiol. 10: 85-92, 1970[Medline]. |
| 3. | Bennet, E. D., M. I. V. Jayson, D. Rubenstein, and E. J. M. Campbell. The ability of man to detect non-elastic loads to breathing. Clin. Sci. (Lond.) 23: 155-162, 1962. |
| 4. | Borg, G. V. Psychophysical bases of perceived exertion. Med. Sci. Sports Exerc. 14: 377-381, 1982[Medline]. |
| 5. | Buchner, H., T. D. Waberski, M. Fuchs, R. Drenckhahn, M. Wagner, and H.-A. Wischmann. Postcentral origin of P22: evidence from source reconstruction in a realistically shaped head model and from a patient with a postcentral lesion. Electroencephalogr. Clin. Neurophysiol. 100: 332-342, 1996[Medline]. |
| 6. | Burki, N. K., P. W. Davenport, F. Safdar, and F. W. Zechman. The effect of airway anesthesia on magnitude estimation of added inspiratory resistive and elastic loads. Am. Rev. Respir. Dis. 127: 2-4, 1983[Medline]. |
| 7. |
Butler, J. E.,
D. K. McKenzie,
M. R. Crawford,
and
S. C. Gandevia.
Role of airway receptors in the reflex responses of human inspiratory muscles to airway occlusion.
J. Physiol. (Lond.)
487:
273-281,
1995 |
| 8. | Campbell, E. J. M., S. Freedman, P. S. Smith, and M. E. Taylor. The ability of man to detect added elastic loads to breathing. Clin. Sci. (Lond.) 20: 223-231, 1961. |
| 9. |
Davenport, P. W.,
D. J. Dalziel,
B. Webb,
J. R. Bellah,
and
C. J. Vierck, Jr.
Inspiratory resistive load detection in conscious dogs.
J. Appl. Physiol.
70:
1284-1289,
1991 |
| 10. |
Davenport, P. W.,
W. A. Friedman,
F. J. Thompson,
and
O. Franzén.
Respiratory-related cortical evoked potentials in humans.
J. Appl. Physiol.
60:
1843-1848,
1986 |
| 11. | Davenport, P. W., G. A. Holt, and P. McN. Hill. The effect of increased inspiratory drive on the sensory activation of the cerebral cortex by inspiratory occlusion. In: Respiratory Control: Central and Peripheral Mechanisms, edited by D. F. Speck, M. S. Dekin, and D. T. Frazier. Lexington, KY: Univ. Press of Kentucky, 1992, p. 216-221. |
| 12. |
Davenport, P. W.,
R. Shannon,
A. Mercak,
R. L. Reep,
and
B. G. Lindsey.
Cerebral cortical evoked potentials elicited by cat intercostal muscle mechanoreceptors.
J. Appl. Physiol.
74:
799-804,
1993 |
| 13. | Davenport, P. W., F. J. Thompson, R. L. Reep, and A. N. Freed. Projection of the phrenic nerve afferents to the cat sensorimotor cortex. Brain Res. 328: 150-153, 1985[Medline]. |
| 14. | Franzén, O., and K. Offenloch. Evoked response correlates of psychophysical magnitude estimates for tactile stimulation in man. Exp. Brain Res. 8: 1-18, 1969[Medline]. |
| 15. | Gliner, J. A., L. J. Folinsbee, and S. M. Horvath. Accuracy and precision of matching inspired lung volume. Percept. Psychophysiol. 29: 511-515, 1981[Medline]. |
| 16. | Hashimoto, I., T. Gatayama, M. Tamaki, R. Ushijima, K. Yoshikawa, M. Sasaki, M. Nomura, and H. Isojima. Multi-unit activity in sensory fibers is related to intensity of sensation evoked by air-puff stimulation of the glabrous hand in man. Electroencephal. Clin. Neurophysiol. 81: 466-472, 1991[Medline]. |
| 17. | Järvilehto, T., H. Hämäläinen, and K. Soininen. Peripheral neural basis of tactile sensations in man. II. Characteristics of human mechanoreceptors in the hairy skin and correlations of their activity with tactile sensations. Brain Res. 219: 13-27, 1981[Medline]. |
| 18. |
Killian, K. J.,
D. D. Bucens,
and
E. J. M. Campbell.
Effect of breathing patterns on the perceived magnitude of added loads to breathing.
J. Appl. Physiol.
52:
578-584,
1982 |
| 19. |
Revelette, W. R.,
and
P. W. Davenport.
Effects of timing of inspiratory occlusion on cerebral evoked potentials in humans.
J. Appl. Physiol.
68:
282-288,
1990 |
| 20. | Rossini, P. M., G. Deuschl, V. Pizzella, F. Tecchio, A. Pasquarelli, E. Feifel, G. L. Romani, and C. H. Lücking. Topography and sources of electromagnetic cerebral responses to electrical and air-puff stimulation of the hand. Electroencephal. Clin. Neurophysiol. 100: 229-239, 1996[Medline]. |
| 21. |
Strobel, R. J.,
and
J. A. Daubenspeck.
Early and late respiratory-related cortical potentials evoked by pressure pulse stimuli in humans.
J. Appl. Physiol.
74:
1484-1491,
1993 |
| 22. | Stubbing, D. G., K. J. Killian, and E. J. M. Campbell. Does resistive load detection obey Weber's law over a wide range of background resistances? (Abstract) Federation Proc. 40: 386, 1981. |
| 23. | Vallbo, Å. B., and K.-E. Hagbarth. Activity from skin mechanoreceptors recorded percutaneously in awake humans. Exp. Neurol. 21: 270-289, 1968[Medline]. |
| 24. | Wiley, R. L., and F. W. Zechman. Perception of added airflow resistance in humans. Respir. Physiol. 2: 73-87, 1966[Medline]. |
| 25. |
Wolkove, N.,
M. D. Altose,
S. G. Kelsen,
P. G. Kondapalli,
and
N. S. Cherniack.
Perception of changes in breathing in normal human subjects.
J. Appl. Physiol.
50:
78-83,
1981 |
| 26. | Zechman, F. W., Jr., and R. L. Wiley. Afferent inputs to breathing: respiratory sensation. In: Handbook of Physiology. The Respiratory System. Control of Breathing. Bethesda, MD: Am. Physiol. Soc., 1986, sect. 3, vol. II, pt. 1, chapt. 14, p. 449-474. |
| 27. | Zhu, Y., and A. Starr. Magnetic stimulation of muscle evokes cerebral potentials. Muscle Nerve 14: 721-732, 1991[Medline]. |
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