Is Disturbed Intracortical Excitability a Stable Trait of Chronic Insomnia? A Study Using Transcranial Magnetic Stimulation Before and After Multimodal Sleep Therapy

doi:10.1016/j.biopsych.2010.06.028

Biological Psychiatry

Volume 68, Issue 10, 15 November 2010, Pages 950-955

https://doi.org/10.1016/j.biopsych.2010.06.028 Get rights and content

Background

Chronic insomnia is a poorly understood disorder. Risk factors for developing chronic insomnia are largely unknown, yet disturbances in brain indexes of arousal seem to accompany the disorder. We here investigate whether insomnia patients and control participants differ with respect to brain responses to direct stimulation, i.e., cortical excitability. Transcranial magnetic stimulation (TMS) offers a method to directly investigate the excitability level of the human cerebral cortex in psychiatric and neurological disease.

Methods

We investigated cortical excitability in 16 insomnia patients and 14 carefully matched control participants using absolute and relative amplitudes of motor evoked potentials in response to single- and paired-pulse stimulation using TMS.

Results

Nonmedicated insomnia patients showed, first, an exaggerated absolute response to both suprathreshold single- and paired-pulse stimulation compared with control participants and second, a reduced relative response to paired-pulse stimulation at long interpulse intervals (i.e., a reduced intracortical facilitation). The abnormal excitability persisted despite sleep therapy that effectively improved sleep quality as well as behavioral and neuroimaging indexes of brain function.

Conclusions

The results suggest that a subtly disturbed intracortical excitability characterizes patients with chronic insomnia: a relatively reduced intracortical facilitation in the context of a globally increased absolute excitability. The findings do not resemble TMS findings after sleep deprivation or in sleep apnea and thus seem specific to insomnia. They may offer diagnostic value and implications for assessment of risk to develop this common and disabling disorder.

Section snippets

Methods and Materials

All procedures complied with the declaration of Helsinki and approval was obtained from the medical ethical committee of the VU University Medical Centre.

Resting Motor Thresholds and Responses to Single-Pulse Stimulation

Insomnia patients and control participants did not differ in their resting motor threshold (51.8 ± 1.2 and 54.1 ± 2.3 of percent stimulator output, mean ± SEM, respectively; p = .35). They did, however, differ in their response to single-pulse suprathreshold stimuli, i.e., 120% of resting motor threshold: the area under the curve of the MEP for insomnia patients was 1511.4 ± 208.6 versus 790.0 ± 128.0 microvolts per millisecond for the control subjects (unpaired t test: p = .008). This

Discussion

Our study demonstrates that patients with chronic insomnia show an increase in excitability, as evidenced by larger MEP sizes to both single-pulse and paired-pulse TMS compared with control participants without sleep complaints. This indicates a stronger recruitment of the MEP, i.e., the increase of the MEP size when the stimulation intensity rises from 100% to 120% of resting motor threshold, which itself did not differ between the two groups. As the MEP size reflects the number of motor units

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Archival ReportIs Disturbed Intracortical Excitability a Stable Trait of Chronic Insomnia? A Study Using Transcranial Magnetic Stimulation Before and After Multimodal Sleep Therapy

Background

Methods

Results

Conclusions

Section snippets

Methods and Materials

Resting Motor Thresholds and Responses to Single-Pulse Stimulation

Discussion

Exp Gerontol

J Psychosom Res

Sleep Med Rev

Biol Psychiatry

Lancet Neurol

Clin Neurophysiol

Psychiatry Res

J Psychiatr Res

J Psychiatr Res

Sleep Med Rev

Sleep Med Rev

Sleep Med Rev

Sleep Med

Prog Brain Res

Clin Neurophysiol

Brain Stimul

Clin Neurophysiol

J Neurol Sci

Clin Neurophysiol

Neuroimage

Neurosci Lett

Clin Neurophysiol

NREM sleep EEG frequency spectral correlates of sleep complaints in primary insomnia subtypes

Sleep

Beta/gamma EEG activity in patients with primary and secondary insomnia and good sleeper controls

Sleep

Prefrontal hypoactivation and recovery in insomnia

Sleep

Chronic insomnia and MRI-measured hippocampal volumes: A pilot study

Sleep

Chronic psychophysiological insomnia: Hyperarousal and/or inhibition deficits? An ERPs investigation

Sleep

The hyperarousal model of insomnia: A review of the concept and its evidence

Sleep Med Rev

Sleep loss affects vigilance: Effects of chronic insomnia and sleep therapy

J Sleep Res

Corticocortical inhibition in human motor cortex

J Physiol

Archival Report
Is Disturbed Intracortical Excitability a Stable Trait of Chronic Insomnia? A Study Using Transcranial Magnetic Stimulation Before and After Multimodal Sleep Therapy