Transcript Effect Of Cortisol On Event Related Potential Correlates Of

Effect Of Cortisol On Event Related Potential Correlates Of
Recollection In Healthy Men
1
McAllister-Williams
751.8
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Rugg
R.H.
and M.D.
1 - Department of Psychiatry, University of Newcastle, Newcastle upon Tyne, UK
2 - Institute
of Analysis
Cognitive Neuroscience, University College London, London, UK
Behavioural
Introduction
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Depression is associated with high cortisol and
impaired neuropsychological function1
Healthy subjects administered glucocorticoids have
impaired memory2,3,4
Hypotheses
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Cortisol administration will reversibly impair source
memory (recollection)
F This impairment will be associated with attenuated
recollection-related ERP activity, especially in right frontal
cortex.
F
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commencing evening of day 1
F finishing morning of day 8
F ERP recordings in afternoon of day 8
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Effect of cortisol on recognition
discrimination (pH-pFA)
1.00
p < 0.05
Cort First
Cort Second
Cort First
Cort Second
0.75
0.75
0.50
Second Visit
RTs
Cortisol
Placebo
First Visit
Correct
rejections
1063  248
1179  269
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Second Visit
Hit/hits
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Cort
Plac
500
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0
–
Plac
20 in male voice, 20 in female voice
F Repeat
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Cortisol significantly modulated memory-related ERP
effects
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1003  214
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1082  196
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Study phase
F 40 low frequency words (1-7/million)
word, then state “pleasant”/“unpleasant”,
“active”/“passive” decision based on sex of voice
Test phase (after delay of 5 minutes)
Significant effect of visit on source judgement
accuracy (F(1,12) = 9.74, p < 0.01)
Cortisol significantly reduced recognition accuracy on
visit 2 (t(6) = 2.62, p < 0.025)
Cortisol significantly speeded response times (F(1,12)
= 9.58, p < 0.01)
Significant drug by response (CR vs HH) by ant./post. interaction 500800 ms post stimuli (F(1,13 = 7.42, p < 0.025)
Significant drug by response (CR vs HH) by ant./post. interaction 8001100 ms post stimuli (F(1,13 = 5.02, p < 0.05)
Significant drug by response (CR vs HH) interaction 1100-1400 ms post
stimuli (F(1,13 = 6.12, p < 0.05)
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A
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B
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ERP Analysis
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Words presented on screen for 500 ms
First response ASAP when see word
Second response ASAP when see “?” presented 1000 ms after 1st response
Next trial 1400 ms after 2nd response
EEG recorded from 100ms prior to word presentation to 1400ms post word
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C
D
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F5
T7
C5
FZ
C3
F
F6
CZ
C4
C6
T8
F
TP7
TP8
F
PZ
F
O1
O2
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Words presented on screen for 500 ms
First response ASAP when see word
Second response ASAP when see “?” presented 1000 ms after 1st response
Next trial 1400 ms after 2nd response
EEG recorded from 100ms prior to word presentation to 1400ms post word
0.59uV
-1.46uV
-3.39uV
800-1100
1100-1400
Analysis conducted on all sites on HH-CR amplitude difference rescaled to remove global differences in amplitude
subsidiary analysis on lateral parietal sites 500-800ms and lateral frontal
sites 1100-1400ms
significant hemisphere by site interactions unmodified by an interaction
with drug.
Chronic administration of cortisol to healthy subjects
causes an impairment in verbal recognition memory
and a speeding of response times
The ERP correlates of episodic memory are markedly
affected by cortisol
The hypothesis of attenuated old/new component(s) is
not supported
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29 scalp electrodes (red + blue)
referenced to left mastoid, rereferenced off-line to linked
mastoids
band width 0.03 - 35 Hz
blink corrected using VEOG
Post-hoc analysis used 6 red
sites to examine ant/post and
left/right differences
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1.17uV
cortisol increased the ERP positivity with a differential
effect on ERPs elicited by correct rejections and hit/hits
F These effects were additive with the ‘left parietal’ and ‘right
frontal’ old/new effects
EEG sampling time-locked to
onset of each word at test
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3.28uV
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FP2
5.17uV
Conclusions
Study-test-study-test design
FP1
-2.16uV
No effect of cortisol on left parietal or right frontal
‘old/new’ effects
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80 words presented visually
F Initial old/new judgement
F If old then male/female judgement
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-0.15uV
Spherical spline maps illustrating the scalp topography
of the differences between ERPs to hit/hits and correct
rejections following placebo and cortisol
Topographic analysis revealed significant drug by site
interactions between 500 and 800 ms (F(5.2,67.4) =
2.90, p < 0.025) and 1100 and 1400 ms (F(5.2,68.2) =
2.38, p < 0.05)
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1.34uV
500-800
0.50
First Visit
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1.97uV
recognition probability (pH - pFA)
F source judgement probability (pHH/H)
1000
Cort
3.84uV
Cortisol
24 Hour Urinary Free Cortisol (IU)
p = 0.001
4.66uV
F
24 hour urinary free cortisol from a.m. day 7 to a.m.
day 8
1500
Placebo
Main focus of interest
1.00
2 way cross over, double blind, random and balanced
order experiment in 14 healthy male volunteers
20mg hydrocortisone/placebo for 7 days
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‘Correct rejections’ (CR) - correctly identified new items
‘False alarms’ (FA) - new items identified as old
‘Hits’ (H) - correctly identified old items
‘Misses’ (M) - old items identified as new
‘Hit/Hits’ (HH) - old items with correct sex judgement
‘Hit/Misses’ (HM) - old items with incorrect sex judgement
Effect of cortisol on source
judgement (pHH/H)
Methods
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Responses categorised as:
ERPs following placebo demonstrate the same
‘old/new’ effects as previously reported 5
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Significant response (CR vs HH) by ant./post. by hemisphere interaction
500-800 ms post stimuli (F(1,13) = 13.13, p < 0.005) due to left parietal
positivity of ERPs for hit/hits relative to correct rejections
Significant response(CR vs HH) by ant./post. by hemisphere interaction
11-1400 ms post stimuli (F(1,13) = 15.70, p < 0.005) due to right frontal
positivity of ERPs for hit/hits relative to correct rejections
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The effect of cortisol began around 400 ms after
stimuli presentation and was long lasting
The effect of cortisol on correct rejection ERPs was
widespread across the scalp (Fig. 4A and D)
There was a relative lack of effect of cortisol on ERPs
to hit/hits at frontal sites (Fig 4B and D)
This differential effect of cortisol depending on the
nature of the stimuli led to an apparent reduction in the
frontal ‘old/new’ effect (Fig 4C and 5)
Cortisol modulates neural generators distinct from those
responsible for the old/new ERP effect
References
1. McAllister-Williams R.H., Ferrier I.N., and Young A.H. (1998) Mood and neuropsychological
function in depression: the role of corticosteroids and serotonin. Psychol. Med. 28, 573-584.
2. Young A.H., Sahakian B.J., Robbins T.W., and Cowen P.J. (1999) The effects of chronic
administration of hydrocortisone on cognitive function in normal male volunteers.
Psychopharm. 145, 260-266.
3. Newcomer J.W., Selke G., Melson A.K., Hershey T., Craft S., Richards K., and Alderson A.L.
(1999) Decreased memory performance in healthy humans induced by stress-level cortisol
treatment. Arch. Gen. Psychiatry 56, 527-533.
4. de Quervain D.J.F., Roozendaal B., Nitsch R.M., McGaugh J.L., and Hock C. (2000) Acute
cortisone administration impairs retrieval of long-term declarative memory in humans. Nature
Neurosci. 3, 313-314.
5. Wilding E.L. and Rugg M.D. (1996) An event-related potential study of recognition memory
with and without retrieval of source. Brain 119, 889-905.
Acknowledgements
Work supported by the Medical Research Council (UK)
via a Clinican Scientist Fellowship to RHMcAW.
MDR is supported by the Wellcome Trust