Sleep disturbances are commonly observed in schizophrenia, including in chronic, early-course, and first-episode patients. This has generated considerable interest, both in clinical and research ...endeavors, in characterizing the relationship between disturbed sleep and schizophrenia. Sleep features can be objectively assessed with EEG recordings. Traditionally, EEG studies have focused on sleep architecture, which includes non-REM and REM sleep stages. More recently, numerous studies have investigated alterations in sleep-specific rhythms, including EEG oscillations, such as sleep spindles and slow waves, in individuals with schizophrenia compared with control subjects. In this article, the author reviews state-of-the-art evidence of disturbed sleep in schizophrenia, starting from the relationship between sleep disturbances and clinical symptoms. First, the author presents studies demonstrating abnormalities in sleep architecture and sleep-oscillatory rhythms in schizophrenia and related psychotic disorders, with an emphasis on recent work demonstrating sleep spindles and slow-wave deficits in early-course and first-episode schizophrenia. Next, the author shows how these sleep abnormalities relate to the cognitive impairments in patients diagnosed with schizophrenia and point to dysfunctions in underlying thalamocortical circuits, Ca
channel activity, and GABA-glutamate neurotransmission. Finally, the author discusses some of the next steps needed to further establish the role of altered sleep in schizophrenia, including the need to investigate sleep abnormalities across the psychotic spectrum and to establish their relationship with circadian disturbances, which in turn will contribute to the development of novel sleep-informed treatment interventions.
Schizophrenia is a chronic, often disabling mental illness with a lifetime prevalence of ~1% worldwide, and 2-to-3 times higher mortality rates are reported in schizophrenia patients compared to the ...general population. Although research has been increasingly focusing on identifying novel diagnostic and treatment resources for this illness, the diagnosis of schizophrenia is still based on clinical criteria, which are subjectively assessed and tend to vary across the course of the illness. Endophenotypes are commonly described as molecular, neuropsychological, neuro-imaging, and electrophysiological parameters that are closely associated to the genetic underpinnings of a specific disorder. Putative endophenotypes for psychiatric disorders should: 1) be associated with a specific illness in the population, 2) be heritable, 3) be present regardless of the patients clinical status, 4) co-segregate with the illness within families, and 5) be detected in non-affected family members of psychiatric patients at higher rates than in the general population. Whenever a genetic association is not present, or has not been investigated, the term biomarker is usually preferred. Endophenotypes and biomarkers are stable over time and are largely symptom independent, thus enabling an objective diagnosis of schizophrenia. Furthermore, these measures could be utilized to assess the risk of developing this disorder, and to identify novel pharmacological targets for its treatment. In this article I will present some of the most promising endophenotypes and biological markers of schizophrenia. For each of them, I will briefly describe abnormal findings in schizophrenia patients and, whenever available, in their first-degree relatives. I will then review the ability of each of these measures to identify individuals with schizophrenia (diagnostic value) and to assess the risk for schizophrenia (predictive value). Finally, I will discuss how some of these endophenotypes and biological markers could be utilized to develop novel treatment targets for schizophrenia, as well as to further the current understanding of the neurobiology of this disorder.
Sleep spindles and slow waves are the two main oscillatory activities occurring during NREM sleep. Slow waves are ∼1 Hz, high amplitude, negative-positive deflections that are primarily generated and ...coordinated within the cortex, whereas sleep spindles are 12–16 Hz, waxing and waning oscillations that are initiated within the thalamus and regulated by thalamo-cortical circuits. In healthy subjects, these oscillations are thought to be responsible for the restorative aspects of sleep and have been increasingly shown to be involved in learning, memory and plasticity. Furthermore, deficits in sleep spindles and, to lesser extent, slow waves have been reported in both chronic schizophrenia (SCZ) and early course psychosis patients. In this article, we will first describe sleep spindle and slow wave characteristics, including their putative functional roles in the healthy brain. We will then review electrophysiological, genetic, and cognitive studies demonstrating spindle and slow wave impairments in SCZ and other psychotic disorders, with particularly emphasis on recent findings in early course patients. Finally, we will discuss how future work, including sleep studies in individuals at clinical high risk for psychosis, may help position spindles and slow waves as candidate biomarkers, as well as novel treatment targets, for SCZ and related psychotic disorders.
Sleep spindles are an electroencephalographic (EEG) hallmark of non-rapid eye movement (NREM) sleep and are believed to mediate many sleep-related functions, from memory consolidation to cortical ...development. Spindles differ in location, frequency, and association with slow waves, but whether this heterogeneity may reflect different physiological processes and potentially serve different functional roles remains unclear. Here we used a unique opportunity to record intracranial depth EEG and single-unit activity in multiple brain regions of neurosurgical patients to better characterize spindle activity in human sleep. We find that spindles occur across multiple neocortical regions, and less frequently also in the parahippocampal gyrus and hippocampus. Most spindles are spatially restricted to specific brain regions. In addition, spindle frequency is topographically organized with a sharp transition around the supplementary motor area between fast (13-15 Hz) centroparietal spindles often occurring with slow-wave up-states, and slow (9-12 Hz) frontal spindles occurring 200 ms later on average. Spindle variability across regions may reflect the underlying thalamocortical projections. We also find that during individual spindles, frequency decreases within and between regions. In addition, deeper NREM sleep is associated with a reduction in spindle occurrence and spindle frequency. Frequency changes between regions, during individual spindles, and across sleep may reflect the same phenomenon, the underlying level of thalamocortical hyperpolarization. Finally, during spindles neuronal firing rates are not consistently modulated, although some neurons exhibit phase-locked discharges. Overall, anatomical considerations can account well for regional spindle characteristics, while variable hyperpolarization levels can explain differences in spindle frequency.
Slow-wave activity (SWA), and its coupling with other sleep features, reorganizes cortical circuitry, supporting cognition. This raises the question: can cognition be improved through SWA ...enhancement? SWA enhancement techniques range from behavioral interventions (such as exercise), which have high feasibility but low specificity, to laboratory-based techniques (such as transcranial stimulation), which have high specificity but are less feasible for widespread use. In this review we describe the pathways through which SWA is enhanced. Pathways encompass enhanced neural activity, increased energy metabolism, and endocrine signaling during wakefulness; also direct enhancement during sleep. We evaluate the robustness and practicality of SWA-enhancement techniques, discuss approaches for determining a causal role of SWA on cognition, and present questions to clarify the mechanisms of SWA-dependent cognitive improvements.
NREM sleep contributes to consolidation of memories and restored executive function. The involvement of NREM features in cognition depends on SWA.
Enhancing SWA in older adults and clinical populations with cognitive deficits may effectively improve cognition through sleep.
Techniques promoting energy metabolism (such as exercise) and endocrine signaling (such as growth hormone) are known to enhance SWA and cognition. SWA may therefore mediate the link between these approaches and cognition.
Brain and body heating, and transcranial stimulation during sleep, are promising approaches to identify the functions of SWA that improve cognition.
•An overview of TMS-EEG methodology and neurophysiological derivations.•A comprehensive review of TMS-EEG as a clinical tool to study healthy and disease brain states.•A discussion of current ...challenges in the field of TMS-EEG and recommendations for future studies.
Concurrent transcranial magnetic stimulation and electroencephalography (TMS–EEG) has emerged as a powerful tool to non-invasively probe brain circuits in humans, allowing for the assessment of several cortical properties such as excitability and connectivity. Over the past decade, this technique has been applied to various clinical populations, enabling the characterization and development of potential TMS–EEG predictors and markers of treatments and of the pathophysiology of brain disorders. The objective of this article is to present a comprehensive review of studies that have used TMS–EEG in clinical populations and to discuss potential clinical applications. To provide a technical and theoretical framework, we first give an overview of TMS–EEG methodology and discuss the current state of knowledge regarding the use of TMS–EEG to assess excitability, inhibition, plasticity and connectivity following neuromodulatory techniques in the healthy brain. We then review the insights afforded by TMS–EEG into the pathophysiology and predictors of treatment response in psychiatric and neurological conditions, before presenting recommendations for how to address some of the salient challenges faced in clinical TMS–EEG research. Finally, we conclude by presenting future directions in line with the tremendous potential of TMS–EEG as a clinical tool.
Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) can excite both cortico-cortical and cortico-spinal axons resulting in TMS-evoked potentials (TEPs) and motor-evoked ...potentials (MEPs), respectively. Despite this remarkable difference with other cortical areas, the influence of motor output and its amplitude on TEPs is largely unknown. Here we studied TEPs resulting from M1 stimulation and assessed whether their waveform and spectral features depend on the MEP amplitude. To this aim, we performed two separate experiments. In experiment 1, single-pulse TMS was applied at the same supra-threshold intensity on primary motor, prefrontal, premotor and parietal cortices and the corresponding TEPs were compared by means of local mean field power and time-frequency spectral analysis. In experiment 2 we stimulated M1 at resting motor threshold in order to elicit MEPs characterized by a wide range of amplitudes. TEPs computed from high-MEP and low-MEP trials were then compared using the same methods applied in experiment 1. In line with previous studies, TMS of M1 produced larger TEPs compared to other cortical stimulations. Notably, we found that only TEPs produced by M1 stimulation were accompanied by a late event-related desynchronization (ERD-peaking at ~300 ms after TMS), whose magnitude was strongly dependent on the amplitude of MEPs. Overall, these results suggest that M1 produces peculiar responses to TMS possibly reflecting specific anatomo-functional properties, such as the re-entry of proprioceptive feedback associated with target muscle activation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Source modeling sleep slow waves Murphy, Michael; Riedner, Brady A; Huber, Reto ...
Proceedings of the National Academy of Sciences - PNAS,
02/2009, Letnik:
106, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Slow waves are the most prominent electroencephalographic (EEG) feature of sleep. These waves arise from the synchronization of slow oscillations in the membrane potentials of millions of neurons. ...Scalp-level studies have indicated that slow waves are not instantaneous events, but rather they travel across the brain. Previous studies of EEG slow waves were limited by the poor spatial resolution of EEGs and by the difficulty of relating scalp potentials to the activity of the underlying cortex. Here we use high-density EEG (hd-EEG) source modeling to show that individual spontaneous slow waves have distinct cortical origins, propagate uniquely across the cortex, and involve unique subsets of cortical structures. However, when the waves are examined en masse, we find that there are diffuse hot spots of slow wave origins centered on the lateral sulci. Furthermore, slow wave propagation along the anterior-posterior axis of the brain is largely mediated by a cingulate highway. As a group, slow waves are associated with large currents in the medial frontal gyrus, the middle frontal gyrus, the inferior frontal gyrus, the anterior cingulate, the precuneus, and the posterior cingulate. These areas overlap with the major connectional backbone of the cortex and with many parts of the default network.
Schizophrenia (SCZ) is a complex psychiatric disorder characterized by a wide range of clinical symptoms, including disrupted sleep. In recent years, there has been growing interest in assessing ...alterations in sleep parameters in patients with SCZ. Sleep spindles are brief (0.5–2 s) bursts of 12‐ to 16‐Hz rhythmic electroencephalogram (EEG) oscillatory activity occurring during non‐rapid eye movement (NREM) sleep. Spindles have been implicated in several critical brain functions, including learning, memory and plasticity, and are thought to reflect the integrity of underlying thalamocortical circuits. This review aims to provide an overview of the current research investigating sleep spindles in SCZ. After briefly describing the neurophysiological features of sleep spindles, I will discuss alterations in spindle characteristics observed in SCZ, their associations with the clinical symptomatology of these patients and their putative underlying neuronal and molecular mechanisms. I will then discuss the utility of sleep spindle measures as predictors of treatment response and disease progression. Finally, I will highlight future directions for research in this emerging field, including the prospect of utilizing sleep spindles as neurophysiological biomarkers of SCZ.
Sleep spindles are NREM sleep oscillations that reflect the integrity of underlying thalamocortical circuits and are implicated in learning, memory and plasticity. A reduction in several spindle parameters has been reported in SCZ, including chronic, early course and at‐risk individuals and has been found to be associated with the clinical symptomatology of these patients. This review reports the main spindle findings in SCZ, presents the underlying neural and molecular mechanisms and discusses the prospect of spindles as neurophysiological biomarkers of SCZ.
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