- Email: [email protected]
Evoked response latency recovery cycles: Changes during sleep in man
Life $ejjnc8s Vol, ).2 ]Part I, pp . 241-248 Prin ed n reat r tain
Pergamon Press
EVOKED RESPONSE LATENCY RECOVERY CYCLES : CHANGES DURING SLEEP IN MAN* Marco Amadeo and Charles Shagass Temple University Medical Center and Eastern Pennsylvania Psychiatric Institute Philadelphia, Pennsylvania 19129
(Received 12 July 1972 ; in final form 2 January 1973) SUMMARY Somatosensory evoked response recovery cycles were measured during sleep . Latency recovery of the initial negative response peak during sleep followed a biphasic cycle, different from that of waking . In the first phase, the second response was relatively accelerated ; in the second phase it was slowed . The cycle was less pronounced in stage I REM than in other sleep stages . We have used average evoked potential techniques to investigate central excitability changes during sleep in man .
We measured recovery functions of
somatosensory responses by administering paired stimuli ; varying the interval between the stimuli permits determination of the time course of changes in responsiveness after application of a single, conditioning, stimulus .
Our
data have yielded evidence, reported here, of an unexpected recovery cycle during sleep, which is derived from the measurement of response latency . Although it is known that evoked responses in all sensory modalities change during sleep (1-5), recovery functions have been reported only in animal studies (6-9) .
To our knowledge, latency recovery during sleep has
not previously been investigated in any organism . Methods A constant current source was used for electrical stimulation of the right median nerve at the wrist (pulse duration, 0 .1 msec ; intensity, 10 ma above sensory threshold) .
Ninety single and 90 paired stimuli were presented
*Supported in part by Grant ~IH 12507, National Institute of Mental Health .
241
242
Vol. 12, No . 6
Evoked Response Latency Recovery Cycle
during each averaging sequence ; repetition interval was l sec ; the order of single and paired stimuli was pseudorandomized within blocks of 30 stimulus presentations .
Intervals between stimuli in a pair were :
3, 5, 10, 20, 30,
50, 80, 110 and 140 msec ; one interval was used per sequence .
EEG electrodes
were 6 cm apart in the left parasagittal plane 7 cm from midline ; the posterior lead was 2 cm behind the line from vertex to external auditory meatus .
Sleep
was monitored from the EEG and from standard electrooculographic and submental electrortyographic recordings .
Responses to single stimuli (R1) were stored
in one channel of an averaging computer .
Responses to both paired and unpaired
stimuli were entered into another channel in opposite polarity to permit visualization of the second response (R2=Rl+R2-R1) . There were twelve subjects, four males and eight females, aged 17 to 40 years (median, 23) ; nine were psychiatric patients and three were paid volunteers .
Each subject was tested from two to four nights to obtain at least
one nine-interval recovery cycle for each of the following :
waking ; sleep
stage II ; sleep stages III and IV ; rapid eye movement sleep (stage 1 REM) (10) .
Stages III and IV were combined because it would have required much
more recording time to obtain complete data for each of these stages .
Stim-
.ii were presented continuously for 6 to 8 hours of sleep to avoid waking, although recording was interrupted to deposit averages on digital tape . Sleep stage corresponding to each average was assessed from the polygraph record ; if later review showed a mixture of stages, the average was discarded . Fig . 1 shows typical responses for waking and stage II sleep . concern only the latency of peak 1, which is reliably identifiable . was measured visually, computer .
Our data Latency
using a quantitative cursor program with a PDP-12
Statistical analysis was performed by means of treatment x treat-
ment x subjects analysis of variance, in which the treatments were interstimulus intervals and stage of sleep . were performed (11) .
When F-Ratios were significant, "t"-tests
However, since the assumption of equal correlations was
Vol. 12, No. 6
Evoked Response Latency Recovery Cycle
09
25
SO
243
75 msw
FIG . 1 Somatosensory responses for one subject during waking and stage II sleep . Interstimulus interval, 5 msec . Relative positivity at presumabl active electrode gives upward deflection . Response to first stimulus (Rl~ is sum of 90 sweeps ; response to second stimulus (R2) is sum of 90 sweeps with paired stimuli minus 90 sweeps with unpaired stimuli, i .e ., 90 (R1+R2) -90 (R1) . Broken vertical line drawn downward from peak 1 of waking R1 falls ahead of peak 1 in R1 tracing during sleep (latency 1 msec greater) . Peak 1 of R2 occurs earlier in sleep than in waking record . Note marked differences in wave form of both R1 and R2 in waking and sleep . probably not met by the data, we employed the conservative F-test suggested by Geisser and Greenhouse (12), i .e ., with 12 subjects, degrees of freedom were always taken as 1 and 11, even though there was a much larger number of observations .
Measurements for all available records for a given condition
were averaged for each subject to provide the values used in analysis . Results Table 1 shows mean latencies for the response to the first stimulus (R1) .
The values confirm previously reported (4) systematic latency
increases from waking through stage I REM to slow wave sleep (F,23 .88 ;
244
Evoked Response Latency Recovery Cycle
Vol. 12, No. 6
p0001) . TABLE 1 Mean Peak Latency (msec) of Initial Negative Deflection and Mean Difference Between R2 and Rl in Waking and Different Sleep Stages Rl
R2
All Intervals
3-30 msec
R2-R1
50-140 msec
3-30 msec
50-140 msec
Waking
18 .74
18 .98
18 .68
0 .24
-0 .06
Stage I REM
19 .18
18 .56
19 .59
-0 .62
0 .41
Stage 11
19 .47
18 .80
20 .60
-0 .67
1 .13
Stage III-IV
19 .78
18 .74
20 .58
-1 .04
0 .80
Fig . 2 plots recovery curves in terms of latency differences between R2 and R1 .
The waking curve resembles that found in previous studies (13) .
w U Z W W IL IL
0
U N N
E
U Z W H 0 Q
Z Q w
WAKING STAGE I REM " --+ STAGE 11 STAGE M - 1Z
Z > -2 N
3
5
10
20 30
50
80 110 140
INTERSTIMULUS INTERVAL (msec )
FIG . 2 Mean differences between R2 and R1 latencies of naak 1 for waking and three sleep stages in 12 subjects . Logarithmic scale used for interstimulus intervals on abscissa . The sleep curves differ in shape from the waking curve .
They are biphasic,
Evoked Response Latency Recovery Cycle
Vol . 12, No. 6
24 5
with R2 latencies less than those of Rl for interstimulus intervals up to 30 msec and greater than Rl latencies for intervals between 50 and 110 msec . the 140 msec interval, sleep R2 latencies approached their Rl values .
At
The
significance of curve shape differences across all nine intervals was supported by the stages x intervals interaction term (F,5 .84 ;p< .05) .
Further
analysis was then performed separately upon two portions of the curve, consisting of the 3 to 30 msec and 50 to 140 msec intervals . Table 1 gives mean R2 latency values for each portion and mean differences between R2 and R1 latencies .
Mean R2-Rl latency differences varied
significantly between stages for both early (F,20 .58 ;p< .001) and late (F,6 .55 ; p< .05) intervals .
For the early intervals, R2-R1 difference values during
waking differed from those of all sleep stages (p< .001 by "t"-test) ; the only significant difference between sleep stages occurred between stages III-IV and I REM (p< .05) .
For the late intervals, "t"-tests showed significant differ-
ences between the waking mean R2-Rl difference and the means for stages II (p< .Ol) and III-IV (p< .05), but not from the for stage I REM and stage II differed (p< .05) .
mean for stage I REM ; the means It seems noteworthy that the
magnitude of both phases of the recovery cycle was less in stage I REM than in other sleep stages . Since the latency recovery finding was unexpected, the resolution of our recordings, 1 msec per data point (Fig . 1), was considerably poorer than it could have been had we originally intended to focus upon this phenomenon .
To
some extent the accuracy of our latency values was improved by averaging the measurements of several recordings to produce a single data value, but the number of records entering into such averages varied .
To obtain additional
assurance concerning the reality of the biphasic latency recovery cycle in sleep, two further analyses were carried out .
These analyses were based only
on the first record for each condition obtained for each subject .
First, for
each interval, the R2-R1 differences for waking were subtracted from those
Vol . 12, No. 6
Evoked Response Latency Recovery Cycle
246
for each sleep stage and a treatment x subjects analysis of variance was performed for each stage .
All three analyses give significant treatment effects,
indicative of differences between the waking and sleep recovery curves (p< .05 by the conservative F-ratio criterion) .
Second, we attempted to
depict the relationship between early and late phases of each recovery curve by means of a single number in order to apply the sign test to compare stages . The number used was based on the relative incidence of negative R2-Rl latency difference values for the early (3 to 30 msec) and late (50 to 140 msec) intervals .
For example, if R2 latency was less than that of Rl for one late
interval and four early intervals, the number indicating difference between late and early phases, would be 3 (4 minus 1) .
Larger numbers would result
if R2 latencies cycle from low values for the early intervals to higher values for the late intervals (Fig . 2) .
The sign tests showed greater differ-
ence values for all sleep stages than for waking (p< .01) ; also the differences between phases were less for stage I REM than for stage III-IV (p< .05) .
These
additional data analyses support the conclusion that there is a biphasic latency recovery cycle in sleep which is not present in waking . The biphasic latency recovery cycle appeared to be a repeatable phenomenon ; it was observed regularly in subjects studied during several nights of sleep .
Also, separate statistical analyses of the data for the nine patient
and three nonpatient subjects gave almost identical results, indicating that the findings were not affected by the presence of psychiatric illness . Discussion If slowed transmission from nerve to cortex be considered an inhibitory effect, the prolonged Rl latencies during sleep would reflect such inhibition . Our results showing that, during sleep, transmission is as fast as the waking time for 20 to 30 msec after a conditioning volley (Table 1) suggest that the early phase of the cycle involves a reversal of this inhibition .
The late
phase of the cycle, which shows greater slowing in R2 than in R1, suggests an
Vol . 12, No . 6
Evoked Response Latency Recovery Cycle
247
augmentation of inhibitory activity, maximal about 80 msec after the conditioning volley . Our results may be related speculatively to data from animal studies of amplitude recovery cycles, which reveal two phases of inhibition (14,15) . One phase, short-term inhibition, occurs before 20 msec and is manifest during waking, but not during sleep .
The second phase, long-term inhibition, extend-
ing from 20 to about 200 msec, is present during slow wave sleep, but not during REM sleep and waking .
Our latency recovery data seem to parallel these
observations, appearing to reflect two phases of inhibition which differ in sleep and waking . The initial negative peak measured here has generally been interpreted as a sign of the thalamo-cortical presynaptic volley (16) .
Although latency
recovery data are not available, animal observations indicate that the slowing of R1 latency during sleep is mediated at the thalamus rather than at cuneate nucleus or cortex (17) .
It seems likely, therefore, that the latency recovery
cycle described here reflects variations in excitability mainly at the thalamic level . Acknowledgements We thank Donald A . Overton, Harold Kosoff, Stephen Slepner and Arieh Sternberg for advice and assistance . References 1.
H .L . WILLIAMS, H .D . MORLOCK, J .V . MORLOCK and A . LUBIN, Annals of the New York Academy of Science , 112, 172-181 (1964) .
2.
K .A . KOOI, B .K . BAGCHI and R .N . JORDAN, Annals of the New York Academy of Science , 112, 270-280 (1964) .
3.
E .C . WEITZMAN and H . KREMEN, Electroenceph . clin . Neurophysiol ., 18, 6570 (1965) .
4.
C . SHAGASS and D .M . TRUSTY, Recent Advances in Biological Psychiatry, p . 321-334, Plenum Press, New York (1966) .
248 5.
Evoked Response Latency Recovery Cycle
Vol. 12, No . 6
W .R . GOFF, T . ALLISON, A . SHAPIRO and B .S . ROSNER, Electroenceph . clin . Neurophysiol ., 21, 1-9 (1966) .
6.
E .V . EVARTS, T .C . FLEMING and P .R . HUTTENLOCHER, Amer . J . Physiol ., 199, 373-376 (1960) .
7.
G .F . ROSSI, M .PALESTRINI and G . ROSADINI, Electroenceph . clin . Neuro siol ., 17, 449-450 (1964) .
8.
T . ALLISON, Electroenceph . clin . Neurophysiol ., 18, 131-139 (1965) .
9.
M . PALESTRINI, M . PISANO, G . ROSADINI and G .F . ROSSI, Electroenceph . clin . Neurophysiol ., 19, 276-283 (1965) .
10 .
W . DEMENT and N . KLEITMAN, Electroenceph . clin . Neurophysiol ., 9, 673690 (1957) .
11 .
E .F . LINDQUIST, Design and Analysis of Experiments in Psychology and Education , p . 237-239, Houghton Mifflin, Boston (1956) .
12 . S . GEISSER and W .W . GREENHOUSE, Annals of Mathematical Statistics , 29, 885-891 (1958) . 13 .
C . SHAGASS, Recent Advances in Biological Psychiatry , p . 205-219, Plenum Press, New York (1968) .
14 .
M DEMETRESCU, M . DEMETRESCU and G . IOSIF, Electroenceph . clin . Neuro hp ysiol ., 18, 1-24 (1965) .
15 .
M . DEMETRESCU, M . DEMETRESCU and G . IOSIF, Electroenceph . clin . Neuroh siol ., 20, 450-469 (1966) .
16 .
B .S . ROSNER, W .R . GOFF and T . ALLISON, EEG and Behavior , p . 109-133, Basic Books, Inc ., New York (1963) .
17 .
N . DAGNINO, E . FAVALE, C . LOEB, M . MANFREDI and A . SEITUM, Boll . Soc . It .
Biol .
Sper . , 41, 550-552 (1965) .
Pergamon Press
EVOKED RESPONSE LATENCY RECOVERY CYCLES : CHANGES DURING SLEEP IN MAN* Marco Amadeo and Charles Shagass Temple University Medical Center and Eastern Pennsylvania Psychiatric Institute Philadelphia, Pennsylvania 19129
(Received 12 July 1972 ; in final form 2 January 1973) SUMMARY Somatosensory evoked response recovery cycles were measured during sleep . Latency recovery of the initial negative response peak during sleep followed a biphasic cycle, different from that of waking . In the first phase, the second response was relatively accelerated ; in the second phase it was slowed . The cycle was less pronounced in stage I REM than in other sleep stages . We have used average evoked potential techniques to investigate central excitability changes during sleep in man .
We measured recovery functions of
somatosensory responses by administering paired stimuli ; varying the interval between the stimuli permits determination of the time course of changes in responsiveness after application of a single, conditioning, stimulus .
Our
data have yielded evidence, reported here, of an unexpected recovery cycle during sleep, which is derived from the measurement of response latency . Although it is known that evoked responses in all sensory modalities change during sleep (1-5), recovery functions have been reported only in animal studies (6-9) .
To our knowledge, latency recovery during sleep has
not previously been investigated in any organism . Methods A constant current source was used for electrical stimulation of the right median nerve at the wrist (pulse duration, 0 .1 msec ; intensity, 10 ma above sensory threshold) .
Ninety single and 90 paired stimuli were presented
*Supported in part by Grant ~IH 12507, National Institute of Mental Health .
241
242
Vol. 12, No . 6
Evoked Response Latency Recovery Cycle
during each averaging sequence ; repetition interval was l sec ; the order of single and paired stimuli was pseudorandomized within blocks of 30 stimulus presentations .
Intervals between stimuli in a pair were :
3, 5, 10, 20, 30,
50, 80, 110 and 140 msec ; one interval was used per sequence .
EEG electrodes
were 6 cm apart in the left parasagittal plane 7 cm from midline ; the posterior lead was 2 cm behind the line from vertex to external auditory meatus .
Sleep
was monitored from the EEG and from standard electrooculographic and submental electrortyographic recordings .
Responses to single stimuli (R1) were stored
in one channel of an averaging computer .
Responses to both paired and unpaired
stimuli were entered into another channel in opposite polarity to permit visualization of the second response (R2=Rl+R2-R1) . There were twelve subjects, four males and eight females, aged 17 to 40 years (median, 23) ; nine were psychiatric patients and three were paid volunteers .
Each subject was tested from two to four nights to obtain at least
one nine-interval recovery cycle for each of the following :
waking ; sleep
stage II ; sleep stages III and IV ; rapid eye movement sleep (stage 1 REM) (10) .
Stages III and IV were combined because it would have required much
more recording time to obtain complete data for each of these stages .
Stim-
.ii were presented continuously for 6 to 8 hours of sleep to avoid waking, although recording was interrupted to deposit averages on digital tape . Sleep stage corresponding to each average was assessed from the polygraph record ; if later review showed a mixture of stages, the average was discarded . Fig . 1 shows typical responses for waking and stage II sleep . concern only the latency of peak 1, which is reliably identifiable . was measured visually, computer .
Our data Latency
using a quantitative cursor program with a PDP-12
Statistical analysis was performed by means of treatment x treat-
ment x subjects analysis of variance, in which the treatments were interstimulus intervals and stage of sleep . were performed (11) .
When F-Ratios were significant, "t"-tests
However, since the assumption of equal correlations was
Vol. 12, No. 6
Evoked Response Latency Recovery Cycle
09
25
SO
243
75 msw
FIG . 1 Somatosensory responses for one subject during waking and stage II sleep . Interstimulus interval, 5 msec . Relative positivity at presumabl active electrode gives upward deflection . Response to first stimulus (Rl~ is sum of 90 sweeps ; response to second stimulus (R2) is sum of 90 sweeps with paired stimuli minus 90 sweeps with unpaired stimuli, i .e ., 90 (R1+R2) -90 (R1) . Broken vertical line drawn downward from peak 1 of waking R1 falls ahead of peak 1 in R1 tracing during sleep (latency 1 msec greater) . Peak 1 of R2 occurs earlier in sleep than in waking record . Note marked differences in wave form of both R1 and R2 in waking and sleep . probably not met by the data, we employed the conservative F-test suggested by Geisser and Greenhouse (12), i .e ., with 12 subjects, degrees of freedom were always taken as 1 and 11, even though there was a much larger number of observations .
Measurements for all available records for a given condition
were averaged for each subject to provide the values used in analysis . Results Table 1 shows mean latencies for the response to the first stimulus (R1) .
The values confirm previously reported (4) systematic latency
increases from waking through stage I REM to slow wave sleep (F,23 .88 ;
244
Evoked Response Latency Recovery Cycle
Vol. 12, No. 6
p0001) . TABLE 1 Mean Peak Latency (msec) of Initial Negative Deflection and Mean Difference Between R2 and Rl in Waking and Different Sleep Stages Rl
R2
All Intervals
3-30 msec
R2-R1
50-140 msec
3-30 msec
50-140 msec
Waking
18 .74
18 .98
18 .68
0 .24
-0 .06
Stage I REM
19 .18
18 .56
19 .59
-0 .62
0 .41
Stage 11
19 .47
18 .80
20 .60
-0 .67
1 .13
Stage III-IV
19 .78
18 .74
20 .58
-1 .04
0 .80
Fig . 2 plots recovery curves in terms of latency differences between R2 and R1 .
The waking curve resembles that found in previous studies (13) .
w U Z W W IL IL
0
U N N
E
U Z W H 0 Q
Z Q w
WAKING STAGE I REM " --+ STAGE 11 STAGE M - 1Z
Z > -2 N
3
5
10
20 30
50
80 110 140
INTERSTIMULUS INTERVAL (msec )
FIG . 2 Mean differences between R2 and R1 latencies of naak 1 for waking and three sleep stages in 12 subjects . Logarithmic scale used for interstimulus intervals on abscissa . The sleep curves differ in shape from the waking curve .
They are biphasic,
Evoked Response Latency Recovery Cycle
Vol . 12, No. 6
24 5
with R2 latencies less than those of Rl for interstimulus intervals up to 30 msec and greater than Rl latencies for intervals between 50 and 110 msec . the 140 msec interval, sleep R2 latencies approached their Rl values .
At
The
significance of curve shape differences across all nine intervals was supported by the stages x intervals interaction term (F,5 .84 ;p< .05) .
Further
analysis was then performed separately upon two portions of the curve, consisting of the 3 to 30 msec and 50 to 140 msec intervals . Table 1 gives mean R2 latency values for each portion and mean differences between R2 and R1 latencies .
Mean R2-Rl latency differences varied
significantly between stages for both early (F,20 .58 ;p< .001) and late (F,6 .55 ; p< .05) intervals .
For the early intervals, R2-R1 difference values during
waking differed from those of all sleep stages (p< .001 by "t"-test) ; the only significant difference between sleep stages occurred between stages III-IV and I REM (p< .05) .
For the late intervals, "t"-tests showed significant differ-
ences between the waking mean R2-Rl difference and the means for stages II (p< .Ol) and III-IV (p< .05), but not from the for stage I REM and stage II differed (p< .05) .
mean for stage I REM ; the means It seems noteworthy that the
magnitude of both phases of the recovery cycle was less in stage I REM than in other sleep stages . Since the latency recovery finding was unexpected, the resolution of our recordings, 1 msec per data point (Fig . 1), was considerably poorer than it could have been had we originally intended to focus upon this phenomenon .
To
some extent the accuracy of our latency values was improved by averaging the measurements of several recordings to produce a single data value, but the number of records entering into such averages varied .
To obtain additional
assurance concerning the reality of the biphasic latency recovery cycle in sleep, two further analyses were carried out .
These analyses were based only
on the first record for each condition obtained for each subject .
First, for
each interval, the R2-R1 differences for waking were subtracted from those
Vol . 12, No. 6
Evoked Response Latency Recovery Cycle
246
for each sleep stage and a treatment x subjects analysis of variance was performed for each stage .
All three analyses give significant treatment effects,
indicative of differences between the waking and sleep recovery curves (p< .05 by the conservative F-ratio criterion) .
Second, we attempted to
depict the relationship between early and late phases of each recovery curve by means of a single number in order to apply the sign test to compare stages . The number used was based on the relative incidence of negative R2-Rl latency difference values for the early (3 to 30 msec) and late (50 to 140 msec) intervals .
For example, if R2 latency was less than that of Rl for one late
interval and four early intervals, the number indicating difference between late and early phases, would be 3 (4 minus 1) .
Larger numbers would result
if R2 latencies cycle from low values for the early intervals to higher values for the late intervals (Fig . 2) .
The sign tests showed greater differ-
ence values for all sleep stages than for waking (p< .01) ; also the differences between phases were less for stage I REM than for stage III-IV (p< .05) .
These
additional data analyses support the conclusion that there is a biphasic latency recovery cycle in sleep which is not present in waking . The biphasic latency recovery cycle appeared to be a repeatable phenomenon ; it was observed regularly in subjects studied during several nights of sleep .
Also, separate statistical analyses of the data for the nine patient
and three nonpatient subjects gave almost identical results, indicating that the findings were not affected by the presence of psychiatric illness . Discussion If slowed transmission from nerve to cortex be considered an inhibitory effect, the prolonged Rl latencies during sleep would reflect such inhibition . Our results showing that, during sleep, transmission is as fast as the waking time for 20 to 30 msec after a conditioning volley (Table 1) suggest that the early phase of the cycle involves a reversal of this inhibition .
The late
phase of the cycle, which shows greater slowing in R2 than in R1, suggests an
Vol . 12, No . 6
Evoked Response Latency Recovery Cycle
247
augmentation of inhibitory activity, maximal about 80 msec after the conditioning volley . Our results may be related speculatively to data from animal studies of amplitude recovery cycles, which reveal two phases of inhibition (14,15) . One phase, short-term inhibition, occurs before 20 msec and is manifest during waking, but not during sleep .
The second phase, long-term inhibition, extend-
ing from 20 to about 200 msec, is present during slow wave sleep, but not during REM sleep and waking .
Our latency recovery data seem to parallel these
observations, appearing to reflect two phases of inhibition which differ in sleep and waking . The initial negative peak measured here has generally been interpreted as a sign of the thalamo-cortical presynaptic volley (16) .
Although latency
recovery data are not available, animal observations indicate that the slowing of R1 latency during sleep is mediated at the thalamus rather than at cuneate nucleus or cortex (17) .
It seems likely, therefore, that the latency recovery
cycle described here reflects variations in excitability mainly at the thalamic level . Acknowledgements We thank Donald A . Overton, Harold Kosoff, Stephen Slepner and Arieh Sternberg for advice and assistance . References 1.
H .L . WILLIAMS, H .D . MORLOCK, J .V . MORLOCK and A . LUBIN, Annals of the New York Academy of Science , 112, 172-181 (1964) .
2.
K .A . KOOI, B .K . BAGCHI and R .N . JORDAN, Annals of the New York Academy of Science , 112, 270-280 (1964) .
3.
E .C . WEITZMAN and H . KREMEN, Electroenceph . clin . Neurophysiol ., 18, 6570 (1965) .
4.
C . SHAGASS and D .M . TRUSTY, Recent Advances in Biological Psychiatry, p . 321-334, Plenum Press, New York (1966) .
248 5.
Evoked Response Latency Recovery Cycle
Vol. 12, No . 6
W .R . GOFF, T . ALLISON, A . SHAPIRO and B .S . ROSNER, Electroenceph . clin . Neurophysiol ., 21, 1-9 (1966) .
6.
E .V . EVARTS, T .C . FLEMING and P .R . HUTTENLOCHER, Amer . J . Physiol ., 199, 373-376 (1960) .
7.
G .F . ROSSI, M .PALESTRINI and G . ROSADINI, Electroenceph . clin . Neuro siol ., 17, 449-450 (1964) .
8.
T . ALLISON, Electroenceph . clin . Neurophysiol ., 18, 131-139 (1965) .
9.
M . PALESTRINI, M . PISANO, G . ROSADINI and G .F . ROSSI, Electroenceph . clin . Neurophysiol ., 19, 276-283 (1965) .
10 .
W . DEMENT and N . KLEITMAN, Electroenceph . clin . Neurophysiol ., 9, 673690 (1957) .
11 .
E .F . LINDQUIST, Design and Analysis of Experiments in Psychology and Education , p . 237-239, Houghton Mifflin, Boston (1956) .
12 . S . GEISSER and W .W . GREENHOUSE, Annals of Mathematical Statistics , 29, 885-891 (1958) . 13 .
C . SHAGASS, Recent Advances in Biological Psychiatry , p . 205-219, Plenum Press, New York (1968) .
14 .
M DEMETRESCU, M . DEMETRESCU and G . IOSIF, Electroenceph . clin . Neuro hp ysiol ., 18, 1-24 (1965) .
15 .
M . DEMETRESCU, M . DEMETRESCU and G . IOSIF, Electroenceph . clin . Neuroh siol ., 20, 450-469 (1966) .
16 .
B .S . ROSNER, W .R . GOFF and T . ALLISON, EEG and Behavior , p . 109-133, Basic Books, Inc ., New York (1963) .
17 .
N . DAGNINO, E . FAVALE, C . LOEB, M . MANFREDI and A . SEITUM, Boll . Soc . It .
Biol .
Sper . , 41, 550-552 (1965) .