Elsevier

Sleep Medicine Reviews

Volume 16, Issue 4, August 2012, Pages 389-394
Sleep Medicine Reviews

Theoretical review
Does abnormal non-rapid eye movement sleep impair declarative memory consolidation?: Disturbed thalamic functions in sleep and memory processing

https://doi.org/10.1016/j.smrv.2011.08.001Get rights and content

Summary

Non-rapid eye movement (NREM) sleep has recently garnered support for its role in consolidating hippocampus-based declarative memories in humans. We provide a brief review of the latest research on NREM sleep activity and its association with declarative memory consolidation. Utilizing empirical findings from sleep studies on schizophrenia, Alzheimer’s disease, and fibromyalgia, we argue that a significant reduction of slow-wave sleep and sleep spindle activity contribute to the development of deficits in declarative memory consolidation along with concomitant sleep disturbances commonly experienced in the aforementioned disorders. A tentative model is introduced to describe the mediating role of the thalamocortical network in disruptions of both declarative memory consolidation and NREM sleep. The hope is to stimulate new research in further investigating the intimate link between these two very important functions.

Introduction

Sleep and memory researchers have extensively investigated sleep processes and their consolidating effects on memory. Many studies focused on the role of rapid-eye movement (REM) sleep in cognitive procedural memory.1 More recently, non-rapid eye movement (NREM) sleep has garnered support for its role in hippocampus-based declarative memory consolidation in humans. Although significant advances have been made in understanding the mechanism driving sleep-dependent memory consolidation, it remains unclear as to what occurs when that mechanism becomes dysfunctional. This paper attempts to take an in depth look at the pathological processes underlying abnormal NREM sleep activity and its possible link to declarative memory impairment. A theoretical model is generated to explain the potential relationship between abnormal electroencephalogram activity found during NREM sleep and co-occurring declarative memory impairment, mediated by thalamocortical network dysfunction. Empirical findings from studies on patients with schizophrenia, Alzheimer’s disease, and fibromyalgia syndrome are utilized to provide substantial support for the proposed model. In addition, we explore the phenomena of disturbed sleep, which is prevalent within the aforementioned patient populations, and how it may be concomitant with, or a risk factor for declarative memory impairment. Before introducing our model a brief review of the significance of NREM sleep on declarative memory consolidation is provided. By reviewing the literature on this relatively new and rapidly growing area of interest, our hope is to stimulate new research in further investigating the possible association between abnormal sleep processes and memory impairment.

Section snippets

NREM sleep and declarative memory

NREM sleep has been established to play a significant role in restoration of physiological functions.2, 3 However, relatively recent within the history of sleep research it has been discovered to serve an additional and equally important function, that of memory consolidation. First, it is necessary to define NREM sleep based on the latest definition. It consists of three stages referred to as stages N1, N2, and N3.4 Stage N1 is characterized by low amplitude mixed frequency (4–7 Hz) activity,

Decreases in SWS and sleep spindle activity associated with declarative memory impairment

There is a growing body of evidence suggesting that memory deficits in a wide range of neuropsychiatric disorders may be related to problems with SWS and spindle functioning. Schizophrenia serves as a prime example. Individuals with schizophrenia present with symptoms of hallucinations, delusions, thought disorder, emotional flattening, and social withdrawal. The characterized neuropathology include dysfunctional inhibitory neuronal circuits, reduced cortical neuropil, and disproportionately

Thalamic functioning in sleep spindle generation and declarative memory consolidation

Describing the neurophysiologic mechanisms underlying the complex network between NREM sleep regulation and declarative memory consolidation may shed further light as to what may be happening during such network dysfunction. The thalamus, a key brain structure within this network, constitutes the main portion of the diencephalon and serves multiple functions including the relay of sensory information through the thalamocortical network to various parts of the neocortex. It contributes to the

Thalamic abnormalities associated with declarative memory impairment and sleep disturbances

Thalamic lesions contribute to deficits in explicit memory wherein the size of the lesion directly relates to long-term explicit memory performance.65 Furthermore, lesioning the anterior thalamus has resulted in direct and negative effects on neuronal integrity and learning.66 Thus, thalamic pathology concomitant with hippocampal dysfunction may provide a possible neurophysiologic basis for declarative memory impairment seen in specific populations.67 Co-occurring sleep disturbances would

Future research and implications

Studies should investigate the risk for declarative memory impairment in individuals within the general population who evidence similar abnormal EEG activity during NREM sleep as previously described. An important inquiry to be made is whether a natural disposition for shortened SWS and reduced spindle activity in a non-patient population can accurately predict poor declarative memory functioning. The previous investigations mentioned regarding age-related declines in NREM sleep activity and

Conclusion

Indeed, the significant role of NREM sleep in memory consolidation has been firmly established. However, theories on the sequelae of NREM sleep dysfunction within the neuropsychiatrically disordered population have been only a budding endeavor. Drawing from research conducted on patients with schizophrenia, AD, and FMS it is suggested that abnormal EEG activity during NREM sleep is, in part, associated with co-occurring declarative memory impairment and sleep disruption. Furthermore, structural

References (95)

  • R. Göder et al.

    Impairment of visuospatial memory is associated with decreased slow wave sleep in schizophrenia

    J Psychiatr Res

    (2004)
  • P.B. Wood et al.

    Reduced presynaptic dopamine activity in fibromyalgia syndrome demonstrated with positron emission tomography: a pilot study

    J Pain

    (2007)
  • N.I. Landrø et al.

    Memory functioning in patients with primary fibromyalgia and major depression and healthy controls

    J Psychosom Res

    (1997)
  • K. Crowley et al.

    The effects of normal aging on sleep spindle and k-complex production

    Clin Neurophysiol

    (2002)
  • A. Nicolas et al.

    Sleep spindle characteristics in healthy subjects of different age groups

    Clin Neurophysiol

    (2001)
  • V. Crunelli et al.

    Thalamic T-type Ca2+ channels and NREM sleep

    Cell Calcium

    (2006)
  • A.O. Rossetti et al.

    Transitory sleep spindles impairment in deep cerebral venous thrombosis

    Neurophysiol Clin

    (2005)
  • Y.D. Van Der Werf et al.

    Contributions of thalamic nuclei to declarative memory functioning

    Cortex

    (2003)
  • J.J. Roland et al.

    Blunted hippocampal, but not striatal, acetylcholine efflux parallels learning impairment in diencephalic-lesioned rats

    Neurobiol Learn Mem

    (2007)
  • T.T. Dang-Vu et al.

    Spontaneous brain rhythms predict sleep stability in the face of noise

    Curr Biol

    (2010)
  • F. Adriano et al.

    Updated meta-analyses reveal thalamus volume reduction in patients with first-episode and chronic schizophrenia

    Schizophr Res

    (2010)
  • J.L. Martin et al.

    Older schizophrenia patients have more disrupted sleep and circadian rhythms than age-matched comparison subjects

    J Psychiatr Res

    (2005)
  • T.L. Jernigan et al.

    Cerebral structure on MRI, part II: specific changes in Alzheimer’s and Huntington’s diseases

    Biol Psychiatry

    (1991)
  • A. Theadom et al.

    Exploring the role of sleep and coping in quality of life in fibromyalgia

    J Psychosom Res

    (2007)
  • I. Oswald

    Sleep

    (1966)
  • J.M. Siegel

    Clues to the functions of mammalian sleep

    Nature

    (2005)
  • C. Iber et al.

    Quan SF for the American Academy of Sleep Medicine. The AASM manual for the scoring of sleep and associated events: Rules, terminology and technical specifications

    (2007)
  • S. Diekelmann et al.

    The memory function of sleep

    Nat Rev Neurosci

    (2010)
  • L.R. Squire et al.

    The medial temporal lobe memory system

    Science

    (1991)
  • T.R. Barrett et al.

    Effect of sleep on memory: III. Controlling for time-of- day effects

    J Exp Psychol

    (1972)
  • M.J. Fowler et al.

    Sleep and memory

    Science

    (1973)
  • W. Plihal et al.

    Effects of early and late nocturnal sleep on declarative and procedural memory

    J Cogn Neurosci

    (1997)
  • M.A. Wilson et al.

    Reactivation of hippocampal ensemble memories during sleep

    Science

    (1994)
  • B. Rasch et al.

    Reactivation and consolidation of memory during sleep

    Curr Dir Psychol Sci

    (2008)
  • B. Rasch et al.

    Odor cues during slow-wave sleep prompt declarative memory consolidation

    Science

    (2007)
  • R. Huber et al.

    Local sleep and learning

    Nature

    (2004)
  • M. Mölle et al.

    Learning increases human electroencephalographic coherence during subsequent slow sleep oscillations

    Proc Natl Acad Sci USA

    (2004)
  • L. Marshall et al.

    Boosting slow oscillations during sleep potentiates memory

    Nature

    (2006)
  • S. Gais et al.

    Learning-dependent increases in sleep spindle density

    J Neurosci

    (2002)
  • M. Schabus et al.

    Sleep spindles and their significance for declarative memory consolidation

    Sleep

    (2004)
  • C. Schmidt et al.

    Encoding difficulty promotes postlearning changes in sleep spindle activity during napping

    J Neurosci

    (2006)
  • J. Tamminen et al.

    Sleep spindle activity is associated with the integration of new memories and existing knowledge

    J Neurosci

    (2010)
  • E.A. Holthausen et al.

    Long-term memory deficits in schizophrenia: primary or secondary dysfunction?

    Neuropsychology

    (2003)
  • M.A. Cirillo et al.

    Verbal declarative memory dysfunction in schizophrenia: from clinical assessment to genetics and brain mechanisms

    Neuropsychol Rev

    (2003)
  • M.S. Keshavan et al.

    Delta sleep deficits in schizophrenia: evidence from automated analyses of sleep data

    Arch Gen Psychiat

    (1998)
  • F. Ferrarelli et al.

    Reduced sleep spindle activity in schizophrenia patients

    Am J Psychiat

    (2007)
  • F. Ferrarelli et al.

    Thalamic dysfunction in schizophrenia suggested by whole-night deficits in slow and fast spindles

    Am J Psychiat

    (2010)
  • Cited by (24)

    • Alterations of sleep oscillations in Alzheimer's disease: A potential role for GABAergic neurons in the cortex, hippocampus, and thalamus

      2022, Brain Research Bulletin
      Citation Excerpt :

      At the thalamic level, this rhythmic firing at delta frequency is derived from the intrinsic voltage-gated ion channels of thalamocortical neurons which promote bursting at delta frequencies when these neurons are hyperpolarized due to the withdrawal of excitatory neuromodulatory inputs and/or increased hyperpolarization from GABAergic neurons, especially from the thalamic reticular nucleus (Jahnsen and Llinas, 1984a, 1984b; Leresche et al., 1990; Lewis et al., 2015; Maquet et al., 1997; Soltesz et al., 1991; Steriade et al., 1993b; Uygun et al., 2022). One of the well-studied functions of SWA is its role in sleep-dependent memory consolidation (Lu and Goder, 2012; Marshall et al., 2006; Steriade and Timofeev, 2003; Walker, 2009). Studies showed that cortical SOs trigger the reactivation of temporarily-stored hippocampal memories in coordination with hippocampal sharp-wave ripples and sleep spindles, which will be reviewed in more detail in the later sections (Diekelmann and Born, 2010; Klinzing et al., 2019; Rasch and Born, 2013).

    • Beta and Gamma Oscillations in Prefrontal Cortex During NMDA Hypofunction: An In Vitro Model of Schizophrenia Features

      2018, Neuroscience
      Citation Excerpt :

      These alterations in the generation of slow rhythms may be linked to the most consistent electrophysiological sleep abnormality reported in schizophrenia, which is a decrease in the amount of slow-wave sleep (for a review see (Keshavan et al., 1990)). These deficits in slow-wave sleep might essentially contribute to the memory impairments detected in schizophrenia (Goder et al., 2008; Manoach and Stickgold, 2009; Lu and Goder, 2012). NMDAr control the firing rate of GABAergic interneurons (Lewis et al., 2005; Homayoun and Moghaddam, 2007), and in fact play a greater role in regulating the spontaneous firing of fast-spiking interneurons than of pyramidal neurons.

    • Quantitative electroencephalogram measures in adult obstructive sleep apnea – Potential biomarkers of neurobehavioural functioning

      2017, Sleep Medicine Reviews
      Citation Excerpt :

      This compromised integrity and vulnerability of the PFC in OSA patients may manifest as altered sleep/wake EEG activity and consequential neurobehavioural dysfunction. It is possible that structural or functional changes in thalamocortical networks may also underlie altered EEG profiles in OSA by compromising the ability to generate specific EEG activity (such as slow oscillations or sleep spindles), resulting in impaired memory consolidation and poor sleep quality but data are lacking (for theoretical review, see Lu and Goder 2012 [101]). OSA and its associated sleep fragmentation and intermittent hypoxemia/hypercapnia may further exacerbate alterations in brain function and structure that naturally occur with ageing [102].

    • Impairment of sleep-related memory consolidation in schizophrenia: Relevance of sleep spindles?

      2015, Sleep Medicine
      Citation Excerpt :

      The underlying cause of this spindle phenotype in schizophrenia is unclear [32]. Thalamic dysfunctions [16,33] were accounted for this, but, since the cortex also plays a crucial role in generating spindles, a cortical contribution to the spindle deficit in schizophrenia is possible [32]. Convenient with the above-mentioned hypotheses about possible functions of sleep spindles, associations between the reduced density of spindles and decreased performance in procedural learning [17] and in our study with impaired sleep-related declarative memory performance were found.

    View all citing articles on Scopus

    The most important references are denoted by an asterisk.

    View full text