SLEEP 2011 Abstract Supplement

A. Basic Science VIII. Behavior
0185
OVERNIGHT THERAPY? SLEEP DE-POTENTIATES
EMOTIONAL BRAIN REACTIVITY
van der Helm E, Yao J, Rao V, Saletin JM, Dutt S, Walker MP
Psychology, University of California Berkeley, Berkeley, CA, USA
Introduction: While the benefit of sleep on various neurocognitive processes
has been established, a role for sleep in emotional brain regulation
remains largely uncharacterized. This is surprising considering that
nearly all clinical mood disorders express co-occurring abnormalities of
sleep, most commonly in the amount and timing of rapid eye movement
(REM) sleep. Using fMRI in combination with EEG sleep physiology,
here we test the hypothesis that sleep, and specific aspects of REM sleep,
de-potentiates the behavioral and neural reactivity associated with prior
affective experiences.
Methods: Thirty-three healthy young adults were randomly assigned
to either the Sleep or Wake group. Both groups performed two fMRI
sessions, separated by a 12hr period containing either a full night of
physiologically recorded sleep (Sleep-group), or a normal waking day
(Wake-group). At each session, participants rated affective picture-stimuli
on a 1-5 scale (corresponding to increasing emotional intensity).
Results: In contrast to equivalent time awake, sleep resulted in a selective
and significant palliative overnight reduction in extreme emotion
intensity ratings (P≤0.04). This behavioral de-potentiation was
further associated with an interaction effect in the amygdala, showing
overnight decreases in reactivity in the Sleep-group (P=0.004), while
no such decrease was observed in the Wake-group. Additionally, this
sleep-dependent reduction in amygdala reactivity was associated with
enhanced ventromedial prefrontal cortex (vmPFC) functional connectivity
(P=0.005). Moreover, the overnight increase in amygdala-vmPFC
connectivity correlated significantly with the speed of entry into REM
sleep (R=0.53, P=0.025). Importantly, no between-group differences in
neural or behavioral reactivity were observed in a circadian-control task,
which entailed rating a novel set of affective pictures, providing a timeof-day
baseline reference.
Conclusion: Taken together, these findings support a homeostatic role
for sleep, and especially REM sleep, in the optimal regulation of limbic
brain networks, de-potentiating next-day emotional reactivity and
re-establishing vmPFC top-down control. Such experimental findings
may hold translational implications for a collection of clinical mood disorders
associated with maladaptive affective reactivity, especially major
depression and PTSD, both of which express concomitant REM sleep
abnormalities and dysfunctional amygdala-PFC emotional activity.
0186
α-1 ADRENOCEPTOR ANTAGONIST PRAZOSIN REDUCES
REM SLEEP (REMS) FRAGMENTATION AND NON-REM
SLEEP (NREMS) LATENCY IN FEAR-CONDITIONED
WISTAR-KYOTO RATS (WKY)
Laitman BM 1 , Gajewski ND 1 , Mann GL 1 , Kubin L 1 , Ross RJ 1,2,3 ,
Morrison AR 1
1
Animal Biology, University of Pennsylvania School of Veterinary
Medicine, Philadelphia, PA, USA, 2 Psychiatry, University of
Pennsylvania School of Medicine, Philadelphia, PA, USA, 3 Behavioral
Health Service, Philadelphia VA Medical Center, Philadelphia, PA,
USA
Introduction: The α-1 adrenoceptor antagonist prazosin reduces nightmares
in posttraumatic stress disorder (PTSD), which has been associated
with REMS fragmentation. Defining REMS fragmentation in rats
as a shift in the distribution of sequential REMS (seq-REMS, inter-
REMS episode interval ≤3 min) and single REMS (si-REMS, inter-
REMS episode interval >3 min) towards seq-REMS, we demonstrated
greater REMS fragmentation following fear conditioning (FC) in WKY
compared to Wistar rats. We hypothesized that prazosin would reduce
FC-elicited REMS fragmentation and other sleep disturbances in WKY.
Methods: Male WKY were habituated and received a prazosin (0.01
mg/kg, i.p.; n=4) or vehicle (n=4) injection followed 15 min later by a
4-h baseline sleep recording. Two days later they were presented with 10
tones (800 Hz, 90 dB, 5 s; 30 s interval), each co-terminating with a foot
shock (1.0 mA, 0.5 s). The following day (Day 1), and again 6 days (Day
7), and 13 days (Day 14) later, prazosin or vehicle was administered, 3
tones were presented without foot shock, and sleep was recorded for 4
h. Waking, NREMS, and REMS were manually scored. Seq-REMS and
si-REMS episodes were distinguished.
Results: WKY given prazosin had a shorter sleep latency (min ±SEM)
on Day 1 (Prazosin: 9.9 ±2.1; Vehicle: 29.0 ±9.1; p=0.01) and a decreased
percentage of seq-REMS relative to total REMS time on Day 14
(Prazosin: 36.3% ±4.5; Vehicle: 67.1% ±6.1; p=0.02).
Conclusion: Prazosin-treated WKY had reduced time to sleep onset
compared to vehicle-treated WKY on Day 1 after FC and, by Day 14,
had reduced REMS fragmentation. Prazosin may facilitate REMS consolidation
in fear-conditioned WKY. These findings strengthen the rationale
for using WKY in the modeling of sleep in PTSD and may lead to
insights into the mechanisms of prazosin action in the disorder.
Support (If Any): Research funded by USPHS Grant MH072897 to
A.R.M.
0187
EXPERIMENTAL SLEEP RESTRICTION IN ADOLESCENTS:
CHANGES IN BEHAVIORAL AND PHYSIOLOGICAL
MEASURES OF EMOTIONAL REACTIVITY
Cousins JC 1 , McMakin D 1 , Dahl R 2 , Forbes E 1 , Silk J 1 , Siegle GJ 1 ,
Franzen PL 1
1
Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA, 2 School of
Public Health, University of California, Berkeley, Berkeley, CA, USA
Introduction: The myriad biological and social changes that occur during
adolescence contribute to later and erratic sleep times and insufficient
sleep. Reduced sleep may impact behavioral, emotional, and social
functioning at this key period of development. We examined how sleep
restriction and sleep extension influenced behavioral and physiological
measures of affective function in adolescents.
Methods: Sixteen healthy adolescents (ages 12-15) were studied in
groups of 2-4 friends during a within-subject sleep restriction manipulation
over two 48-hour laboratory visits, using crossover design. Sleep
restriction consisted of six hours in bed on night 1 and two hours in bed
on night 2. Sleep extension consisted of 10 hours in bed for both nights.
Physiological and behavioral testing occurred on day 2 of each condition.
Responses to positive, negative, and neutral auditory stimuli were
examined with pupil dilation—a physiological measure of emotional
reactivity. Pairs of friends completed a 5-minute videotaped discussion
about resolving a conflict in their relationship. Interactions were coded
for negative and positive affect using the International Dimensions Coding
System-revised (IDCS-R).
Results: Compared to the sleep extension condition, adolescents showed
larger pupil dilation responses to negative sounds relative to neutral
sounds after sleep restriction (M±SD=0.137±.21 mm, and 0.306±.225
mm, respectively; F(1,14)=6.49, p=0.02). Adolescents displayed more
negative affect during peer interactions following sleep restriction
(M±SD=7.3 ±1.8) compared to the well-rested condition (M=6.4±1.2),
F(1,14.9)=5.45, p=0.03. Further, after sleep restriction but not sleep extension,
negative affect during peer interactions was correlated (r2=0.42,
p