Archival Report|Articles in Press

Sleep spindles favor emotion regulation over memory consolidation of stressors in PTSD

Published:March 06, 2023DOI:



      Posttraumatic stress disorder (PTSD) is a trauma-induced condition, characterized by intrusive memories and trauma-associated anxiety. Here, NREM (non-rapid eye movement) sleep spindles might play a crucial role in learning and consolidating declarative stressor information. However, sleep, and possibly sleep spindles, are also known to regulate anxiety, suggestive of a dual role for sleep spindles in the processing of stressors. Specifically, in high PTSD symptom individuals, spindles might fail to regulate anxiety levels after exposure and instead might maladaptively consolidate stressor information.


      To disentangle the role of spindles in declarative memory vs. anxiety regulation after stressor exposure, and to examine the role of PTSD in these processes, we measured nap sleep after a cohort of 45 trauma-exposed subjects were exposed to laboratory stress. Subjects (high vs. low in PTSD symptoms) performed two visits: 1) a stress visit involving exposure to negatively valent images pre-nap and 2) a control visit. In both visits, sleep was monitored via electroencephalography (EEG). A stressor recall session took place post-nap in the stress visit.


      NREM2 spindle rates were higher in stress vs. control sleep indicative of stress-induced changes in spindles. In high-PTSD subjects, NREM2 spindle rates in stress sleep predicted poorer recall accuracy of stressor images relative to low-PTSD subjects, while correlating with a greater reduction in stressor-induced anxiety levels post-sleep.


      Contrary to our expectations, although spindles are known to play a role in declarative memory processes, our findings highlight an important role for spindles in sleep-dependent anxiety regulation in PTSD.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


        • Germain A
        Sleep disturbances as the hallmark of PTSD: where are we now?.
        American Journal of Psychiatry. 2013; 170: 372-382
        • Neylan TC
        • Marmar CR
        • Metzler TJ
        • Weiss DS
        • Zatzick DF
        • Delucchi KL
        • et al.
        Sleep disturbances in the Vietnam generation: findings from a nationally representative sample of male Vietnam veterans.
        American Journal of Psychiatry. 1998; 155: 929-933
        • Ross RJ
        • Ball WA
        • Sullivan KA
        • Caroff SN
        Sleep disturbance as the hallmark of posttraumatic stress disorder.
        The American journal of psychiatry. 1989;
        • Richards A
        • Kanady JC
        • Neylan TC
        Sleep disturbance in PTSD and other anxiety-related disorders: an updated review of clinical features, physiological characteristics, and psychological and neurobiological mechanisms.
        Neuropsychopharmacology. 2020; 45: 55-73
        • Germain A
        • Buysse DJ
        • Nofzinger E
        Sleep-specific mechanisms underlying posttraumatic stress disorder: integrative review and neurobiological hypotheses.
        Sleep medicine reviews. 2008; 12: 185-195
        • Germain A
        • McKeon AB
        • Campbell RL
        Sleep in PTSD: Conceptual model and novel directions in brain-based research and interventions.
        Current opinion in psychology. 2017; 14: 84-89
        • Goldstein AN
        • Walker MP
        The role of sleep in emotional brain function.
        Annual review of clinical psychology. 2014; 10: 679-708
        • Mellman TA
        • Bustamante V
        • Fins AI
        • Pigeon WR
        • Nolan B
        REM sleep and the early development of posttraumatic stress disorder.
        American Journal of Psychiatry. 2002; 159: 1696-1701
        • Marshall AJ
        • Acheson DT
        • Risbrough VB
        • Straus LD
        • Drummond SP
        Fear conditioning, safety learning, and sleep in humans.
        Journal of Neuroscience. 2014; 34: 11754-11760
        • Straus LD
        • Acheson DT
        • Risbrough VB
        • Drummond SP
        Sleep deprivation disrupts recall of conditioned fear extinction.
        Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2017; 2: 123-129
        • Richards A
        • Inslicht SS
        • Yack LM
        • Metzler TJ
        • Russell Huie J
        • Straus LD
        • et al.
        The relationship of fear-potentiated startle and polysomnography-measured sleep in trauma-exposed men and women with and without PTSD: testing REM sleep effects and exploring the roles of an integrative measure of sleep, PTSD symptoms, and biological sex.
        Sleep. 2022; 45: zsab271
        • Gais S
        • Mölle M
        • Helms K
        • Born J
        Learning-dependent increases in sleep spindle density.
        Journal of Neuroscience. 2002; 22: 6830-6834
        • Schabus M
        • Gruber G
        • Parapatics S
        • Sauter C
        • Klösch G
        • Anderer P
        • et al.
        Sleep spindles and their significance for declarative memory consolidation.
        Sleep. 2004; 27: 1479-1485
        • Fernandez LM
        • Lüthi A
        Sleep spindles: mechanisms and functions.
        Physiological reviews. 2020; 100: 805-868
        • Peyrache A
        • Seibt J
        A mechanism for learning with sleep spindles.
        Philosophical Transactions of the Royal Society B. 2020; 37520190230
        • Clemens Z
        • Fabo D
        • Halasz P
        Overnight verbal memory retention correlates with the number of sleep spindles.
        Neuroscience. 2005; 132: 529-535
        • Staresina BP
        • Bergmann TO
        • Bonnefond M
        • Van Der Meij R
        • Jensen O
        • Deuker L
        • et al.
        Hierarchical nesting of slow oscillations, spindles and ripples in the human hippocampus during sleep.
        Nature neuroscience. 2015; 18: 1679-1686
        • Clemens Z
        • Mölle M
        • Erőss L
        • Jakus R
        • Rásonyi G
        • Halász P
        • et al.
        Fine‐tuned coupling between human parahippocampal ripples and sleep spindles.
        European Journal of Neuroscience. 2011; 33: 511-520
        • Lehmann M
        • Schreiner T
        • Seifritz E
        • Rasch B
        Emotional arousal modulates oscillatory correlates of targeted memory reactivation during NREM, but not REM sleep.
        Scientific reports. 2016; 6: 1-13
        • Payne JD
        • Stickgold R
        • Swanberg K
        • Kensinger EA
        Sleep preferentially enhances memory for emotional components of scenes.
        Psychological science. 2008; 19: 781-788
        • Wagner U
        • Hallschmid M
        • Rasch B
        • Born J
        Brief sleep after learning keeps emotional memories alive for years.
        Biological psychiatry. 2006; 60: 788-790
        • Cairney SA
        • Durrant SJ
        • Hulleman J
        • Lewis PA
        Targeted memory reactivation during slow wave sleep facilitates emotional memory consolidation.
        Sleep. 2014; 37: 701-707
        • Kaestner EJ
        • Wixted JT
        • Mednick SC
        Pharmacologically increasing sleep spindles enhances recognition for negative and high-arousal memories.
        Journal of Cognitive Neuroscience. 2013; 25: 1597-1610
        • Wang C
        • Laxminarayan S
        • Ramakrishnan S
        • Dovzhenok A
        • Cashmere JD
        • Germain A
        • et al.
        Increased oscillatory frequency of sleep spindles in combat-exposed veteran men with post-traumatic stress disorder.
        Sleep. 2020; 43: zsaa064
        • Wang C
        • Laxminarayan S
        • Cashmere JD
        • Germain A
        • Reifman J
        Inter-channel phase differences during sleep spindles are altered in Veterans with PTSD.
        NeuroImage: Clinical. 2020; 28102390
      1. van der Heijden AC, Hofman WF, de Boer M, Nijdam MJ, van Marle HJF, Jongedijk RA, et al. (2022): Sleep spindle dynamics suggest over-consolidation in post-traumatic stress disorder. Sleep.

        • Kleim B
        • Wysokowsky J
        • Schmid N
        • Seifritz E
        • Rasch B
        Effects of sleep after experimental trauma on intrusive emotional memories.
        Sleep. 2016; 39: 2125-2132
        • Gruber R
        • Cassoff J
        The interplay between sleep and emotion regulation: conceptual framework empirical evidence and future directions.
        Current psychiatry reports. 2014; 16: 1-9
        • Walker MP
        The role of sleep in cognition and emotion.
        Annals of the New York Academy of Sciences. 2009; 1156: 168-197
        • Wilhelm I
        • Groch S
        • Preiss A
        • Walitza S
        • Huber R
        Widespread reduction in sleep spindle activity in socially anxious children and adolescents.
        Journal of Psychiatric Research. 2017; 88: 47-55
        • Mikoteit T
        • Brand S
        • Beck J
        • Perren S
        • von Wyl A
        • von Klitzing K
        • et al.
        Visually detected NREM Stage 2 sleep spindles in kindergarten children are associated with stress challenge and coping strategies.
        The World Journal of Biological Psychiatry. 2012; 13: 259-268
        • Cahill L
        Neurobiological mechanisms of emotionally influenced, long-term memory.
        Progress in brain research. 2000; 126: 29-37
        • Blake DD
        • Weathers FW
        • Nagy LM
        • Kaloupek DG
        • Gusman FD
        • Charney DS
        • et al.
        The development of a clinician-administered PTSD scale.
        Journal of traumatic stress. 1995; 8: 75-90
        • Weathers FW
        • Bovin MJ
        • Lee DJ
        • Sloan DM
        • Schnurr PP
        • Kaloupek DG
        • et al.
        The Clinician-Administered PTSD Scale for DSM–5 (CAPS-5): Development and initial psychometric evaluation in military veterans.
        Psychological assessment. 2018; 30: 383
        • Verschuere B
        • Crombez G
        • Koster E
        The international affective picture system.
        Psycholo Belgica. 2001; 41: 205-217
        • Silversmith DB
        • Lemke SM
        • Egert D
        • Berke JD
        • Ganguly K
        The degree of nesting between spindles and slow oscillations modulates neural synchrony.
        Journal of Neuroscience. 2020; 40: 4673-4684
        • Andrillon T
        • Nir Y
        • Staba RJ
        • Ferrarelli F
        • Cirelli C
        • Tononi G
        • et al.
        Sleep spindles in humans: insights from intracranial EEG and unit recordings.
        Journal of Neuroscience. 2011; 31: 17821-17834
        • Mölle M
        • Bergmann TO
        • Marshall L
        • Born J
        Fast and slow spindles during the sleep slow oscillation: disparate coalescence and engagement in memory processing.
        Sleep. 2011; 34: 1411-1421
        • Cox R
        • Schapiro AC
        • Manoach DS
        • Stickgold R
        Individual differences in frequency and topography of slow and fast sleep spindles.
        Frontiers in human neuroscience. 2017; 11: 433
        • De Gennaro L
        • Ferrara M
        • Vecchio F
        • Curcio G
        • Bertini M
        An electroencephalographic fingerprint of human sleep.
        Neuroimage. 2005; 26: 114-122
        • Pace-Schott EF
        • Germain A
        • Milad MR
        Effects of sleep on memory for conditioned fear and fear extinction.
        Psychological bulletin. 2015; 141: 835
        • Walker MP
        • Stickgold R
        Sleep, memory, and plasticity.
        Annu Rev Psychol. 2006; 57: 139-166
        • Jiang X
        • Gonzalez-Martinez J
        • Halgren E
        Posterior hippocampal spindle ripples co-occur with neocortical theta bursts and downstates-upstates, and phase-lock with parietal spindles during NREM sleep in humans.
        Journal of Neuroscience. 2019; 39: 8949-8968
        • Andrade KC
        • Spoormaker VI
        • Dresler M
        • Wehrle R
        • Holsboer F
        • Sämann PG
        • et al.
        Sleep spindles and hippocampal functional connectivity in human NREM sleep.
        Journal of Neuroscience. 2011; 31: 10331-10339
        • Paré D
        • Collins DR
        • Pelletier JG
        Amygdala oscillations and the consolidation of emotional memories.
        Trends in cognitive sciences. 2002; 6: 306-314
        • Skelin I
        • Zhang H
        • Zheng J
        • Ma S
        • Mander BA
        • McManus OK
        • et al.
        Coupling between slow waves and sharp-wave ripples engages distributed neural activity during sleep in humans.
        Proceedings of the National Academy of Sciences. 2021; 118
        • Cox R
        • Rüber T
        • Staresina BP
        • Fell J
        Sharp wave-ripples in human amygdala and their coordination with hippocampus during NREM sleep.
        Cerebral cortex communications. 2020; 1 (tgaa051)
        • Girardeau G
        • Inema I
        • Buzsáki G
        Reactivations of emotional memory in the hippocampus–amygdala system during sleep.
        Nature neuroscience. 2017; 20: 1634-1642
        • Van der Kolk BA
        The body keeps the score: Memory and the evolving psychobiology of posttraumatic stress.
        Harvard review of psychiatry. 1994; 1: 253-265
        • Van der Kolk BA
        • Hopper JW
        • Osterman JE
        Exploring the nature of traumatic memory: Combining clinical knowledge with laboratory methods.
        Journal of Aggression, Maltreatment & Trauma. 2001; 4: 9-31
        • Ramanathan DS
        • Gulati T
        • Ganguly K
        Sleep-dependent reactivation of ensembles in motor cortex promotes skill consolidation.
        PLoS biology. 2015; 13e1002263
        • Antony JW
        • Paller KA
        Using oscillating sounds to manipulate sleep spindles.
        Sleep. 2017; 40: zsw068