Original ArticleEffect of repetitive transcranial magnetic stimulation on the cognitive impairment induced by sleep deprivation: a randomized trial
Introduction
The problem of sleep deprivation (SD) has attracted widespread attention. From the perspective of individual health, SD is a major cause of a series of diseases, including increased risks of hypertension, diabetes, heart disease and stroke [1]. From a social perspective, SD also increases the incidence of traffic and medical accidents [2,3].
In neuroscience, SD exerts a negative effect on cognitive functions and mood. SD increases the variability in alertness, decreases attention, worsens moods, and decreases memory acquisition and consolidation [4,5].
Although previous studies have investigated the neurophysiological changes occurring within the body resulting from SD, the mechanism underlying the decrease in mood and performance induced by SD has not been clearly elucidated.
SD induces changes in brain metabolism and neural activation (eg, decreases in regional brain activation and cerebral blood flow) [6,7], and alterations in oxy-Hb and deoxy-Hb levels [8]. In addition, some studies have focused on biochemical changes occurring after SD.
The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in regulating physiological responses to stress [9]. While SD affects the neuroendocrine stress systems, it potentially activates the HPA axis, which may induce cognitive impairment [10,11]. Cortisol levels in the blood and saliva increase after 24 h of SD, indicating the hyperactivity of the HPA axis [12,13]. Brain-derived neurotrophic factor (BDNF), a growth factor, plays an important role in synaptogenesis in brain regions. Its neurotrophic functions are relevant to neuroplasticity, memory and sleep [[14], [15], [16], [17]]. SD decreases BDNF levels, which leads to impairments in brain function [11].
As SD exerts many adverse effects, measures designed to maintain cognitive functions (eg, memory and attention) are of increasing importance. In recent years, some studies have investigated drugs and nonpharmacological methods to help people recover from SD [18], and because of the side effects of medication, the effect of noninvasive brain stimulation, such as repetitive transcranial magnetic stimulation (rTMS), on the cognitive impairment induced by SD has become a research hotspot.
Transcranial magnetic stimulation (TMS) is a neurostimulation and neuromodulation technique based on the principle of the electromagnetic induction of an electric field in the brain [19]. SD appears to induce relatively specific changes at the TMS level and therefore some TMS-derived measures of cortical excitability might be viewed both as electrocortical markers of SD and as targets for rTMS [20]. Currently, rTMS is described as a promising noninvasive intervention for people who have experienced SD. According to Luber and colleagues, high-frequency rTMS (HF-rTMS) facilitates the activation of brain regions in sleep-deprived individuals and reduces the SD-induced impairment in working memory [21,22], Meanwhile, another study also showed effects of HF-rTMS on ameliorating the cognitive impairment induced by SD [23]. Therefore, we chose a high frequency of 10 Hz for our study.
However, studies of the effect of rTMS on SD are still limited. The biochemical changes in individuals with SD treated with the rTMS intervention also remain unclear. The present study recruited healthy Chinese people to investigate the changes in cognitive function after SD and to evaluate the effects of rTMS on impaired cognitive function resulting from SD, as well as the mechanism of rTMS. We hypothesized that the application of HF-rTMS during SD might contribute to the recovery of the impaired cognitive function induced by SD.
Section snippets
Participants
This randomized, placebo-controlled, double-blind study was conducted between May 2018 and May 2019 in the Psychiatric Ward of the First Affiliated Hospital, Zhejiang University School of Medicine. On May 20, 2018, the participants were first recruited. The study was approved by the ethics committee of the First Affiliated Hospital of the Medical School of Zhejiang University in accordance with the Declaration of Helsinki (No. 2017631) and was registered in the China Clinical Trial Registry
Results
The two groups were matched by sex. No significant differences were detected in baseline data or demographic characteristics, including age and years of education, of the two groups (See Table 1).
Discussion
As shown in the present study, 24 h of SD impairs cognitive function, induces emotional disturbances, increases the activity of the HPA axis, decreases frontal activation and leads to dysfunction of the BDNF system. HF-rTMS applied to left DLPFC during SD reverses the hyperactivation of the HPA axis, reduced frontal activation and disturbances in the BDNF system. Based on these results, the SD-induced impairment in brain function might be ameliorated by HF-rTMS.
The present study evaluated the
Conclusions
In summary, SD leads to poor mood, impaired cognitive function, hyperactivation of the HPA axis, decreased frontal activation and abnormal function of the BDNF system. Importantly, HF-rTMS during SD reversed the overactivation of the HPA axis and reduced frontal activation. It might help alleviate the cognitive impairment in the long term.
Role of funding source
This work presented here was supported by the Major Subject of Zhejiang Province (grant number 2015C03040 to Yi Xu).
CRediT authorship contribution statement
Shangda Li: Investigation, Formal analysis, Writing - original draft, Writing - review & editing. Hetong Zhou: Validation, Writing - original draft. Yueran Yu: Data curation, Investigation. Hailong Lyu: Software, Writing - original draft. Tingting Mou: Investigation. Gongde Shi: Investigation. Shaohua Hu: Project administration, Writing - review & editing. Manli Huang: Project administration, Writing - review & editing. Jianbo Hu: Project administration, Writing - review & editing. Yi Xu:
Acknowledgement
We thank the participants for entering the experiment. We also thank the staff in the Department of Psychiatry of The First Affiliated Hospital, Zhejiang University School of Medicine for their assistance during the experiment. Finally, we thank Dr Lu Shaojia and Dr Yu Zhebin for kindly helping with the present study.
References (63)
- et al.
Mechanisms of stress: a dynamic overview of hormonal and behavioral homeostasis
Neurosci Biobehav Rev
(1992) - et al.
Restricted and disrupted sleep: effects on autonomic function, neuroendocrine stress systems and stress responsivity
Sleep Med Rev
(2008) - et al.
Influence of sleep deprivation and circadian misalignment on cortisol, inflammatory markers, and cytokine balance
Brain Behav Immun
(2015) - et al.
Does sleep deprivation increase the vulnerability to acute psychosocial stress in young and older adults?
Psychoneuroendocrinology
(2018) Spatially restricted actions of BDNF
Neuron
(2002)- et al.
Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research
Clin Neurophysiol
(2009) - et al.
Distinctive patterns of cortical excitability to transcranial magnetic stimulation in obstructive sleep apnea syndrome, restless legs syndrome, insomnia, and sleep deprivation
Sleep Med Rev
(2015) - et al.
Effect of two weeks of rTMS on brain activity in healthy subjects during an n-back task: a randomized double blind study
Brain Stimul
(2013) - et al.
Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee
Clin Neurophysiol
(2015) - et al.
Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression
Lancet
(1996)
Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: a systematic review and meta-analysis
Brain Cognit
Prefrontal activation in response to emotional words in patients with bipolar disorder and major depressive disorder
Neuroimage
Reduced prefrontal activation during a verbal fluency task in Chinese-speaking patients with schizophrenia as measured by near-infrared spectroscopy
Prog Neuro-Psychopharmacol Biol Psychiatry
Prefrontal activation during a working memory task differs between patients with unipolar and bipolar depression: a preliminary exploratory study
J Affect Disord
Effects of sleep deprivation on Color-Word, Emotional, and Specific Stroop interference and on self-reported anxiety
Brain Cognit
A systematic review and meta-analysis on placebo response to repetitive transcranial magnetic stimulation for depression trials
Prog Neuro-Psychopharmacol Biol Psychiatry
Efficacy and placebo response of repetitive transcranial magnetic stimulation for primary insomnia
Sleep Med
Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014-2018)
Clin Neurophysiol
Does a single neurostimulation session really affect mood in healthy individuals? A systematic review
Neuropsychologia
Could BDNF be involved in compensatory mechanisms to maintain cognitive performance despite acute sleep deprivation? An exploratory study
Int J Psychophysiol
Enhancement of human cognitive performance using transcranial magnetic stimulation (TMS)
Neuroimage
BDNF-induced local protein synthesis and synaptic plasticity
Neuropharmacology
Assessment of Brain Derived Neurotrophic Factor in hair to study stress responses: a pilot investigation
Psychoneuroendocrinology
Antidepressant-like activity of resveratrol treatment in the forced swim test and tail suspension test in mice: the HPA axis, BDNF expression and phosphorylation of ERK
Pharmacol Biochem Behav
Sleepiness, driving, and motor vehicle crashes. Council on scientific affairs, American medical association
JAMA
Neurocognitive consequences of sleep deprivation
Semin Neurol
The role of sleep in learning and memory
Science
Sleep deprivation disrupts prepulse inhibition and induces psychosis-like symptoms in healthy humans
J Neurosci
Chapter 5 - sleep deprivation
Cerebral perfusion differences between drowsy and non drowsy individuals after acute sleep restriction
Sleep
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2023, Behavioural Brain ResearchCitation Excerpt :Besides, some studies revealed that though caffeine could improve sustained attention impaired by SD, it did not elevate behavioral performance with a high cognitive load which is essential for occupational settings [12,15]. Therefore, some non-pharmacological methods, including transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial magnetic stimulation (TMS) are promising [16–20]. These non-invasive electrical/magnetic neuromodulation devices can modulate the excitability of a range of cortical and subcortical regions and demonstrate significant potential in controlling cognition and regulating sleep [16,17].
Repetitive transcranial magnetic stimulation in primary sleep disorders
2023, Sleep Medicine ReviewsCitation Excerpt :The examination of the references from relevant papers did not detect additional articles fitting the purpose of this review. Therefore, a total of 27 papers were eventually included in the present review: 10 in primary CI [59–68], four in OSAS [69–72], five in RLS [73–77], five in SD [78–82], and three in other primary sleep disorders [83–85]. The main findings of rTMS studies in patients with primary CI are summarized in Table 1.
Repetitive TMS for the “cognitive tsunami” of sleep deprivation
2021, Sleep Medicine
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Shangda Li and Hetong Zhou are co-first authors.