title: Is disturbed intracortical excitability a stable trait of chronic insomnia? A study using transcranial magnetic stimulation before and after multimodal sleep therapy.
abstract: 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.
authors: Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands. y.van.der.werf@nin.knaw.nl
authors: Ysbrand D
authors: YD
authors: van der Werf
authors: Ellemarije
authors: E
authors: Altena
authors: Karin D
authors: KD
authors: van Dijk
authors: Rob L M
authors: RL
authors: Strijers
authors: Wim
authors: W
authors: De Rijke
authors: Cornelis J
authors: CJ
authors: Stam
authors: Eus J W
authors: EJ
authors: van Someren
mesh_terms: D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000503:physiopathology*; D003131:Combined Modality Therapy / Q000379:methods*; D019054:Evoked Potentials, Motor / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D007319:Sleep Initiation and Maintenance Disorders / Q000503:physiopathology* / Q000628:therapy*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*