Increased use-dependent plasticity in chronic insomnia

Abstract

Study objectives: During normal sleep several neuroplasticity changes occur, some of which are considered to be fundamental to strengthen memories. Given the evidence linking sleep to neuroplasticity, it is conceivable that individuals with chronic sleep disruption, such as patients with chronic insomnia (CI), would experience abnormalities in neuroplastic processes during daytime. Protocols testing use-dependent plasticity (UDP), one of the mechanisms underlying formation of motor memories traces, provide a sensitive measure to assess neuroplasticity in the context of motor training.

Design and participants: A well-established transcranial magnetic stimulation (TMS) paradigm was used to evaluate the ability of patients with CI and age-matched good sleeper controls to undergo UDP. We also investigated the effect of insomnia on intracortical motor excitability measures reflecting GABAergic and glutamatergic mechanisms.

Setting: Human Brain Physiology Laboratory, Johns Hopkins Medical Institutions.

Measurements and results: We found that patients with CI experienced increased UDP changes relative to controls. This effect was not due to differences in motor training. In addition, patients with CI showed enhanced intracortical facilitation relative to controls, in the absence of changes in intracortical inhibitory measures.

Conclusion: This study provides the first evidence that patients with chronic insomnia have an increased plasticity response to physical exercise, possibly due to larger activation of glutamatergic mechanisms. This suggests a heightened state of neuroplasticity, which may reflect a form of maladaptive plasticity, similar to what has been described in dystonia patients and chronic phantom pain after amputation. These results could lead to development of novel treatments for chronic insomnia.

Keywords: Insomnia; memory; motor training; plasticity; transcranial magnetic stimulation.

Figure 1

Schematic representation of the experiment setup. Session 1 (i.e., UDP Measures): at baseline (Pre) TMS-evoked movement directions were derived from the first-peak acceleration in the 2 major axes of the movement (extension/flexion and abduction/adduction) recorded by an accelerometer mounted on the proximal phalanx of the thumb. Black arrows indicate the direction of individual TMS-evoked thumb movements (in this case extension and abduction). Motor training was then completed for 30 min, where voluntary thumb movements were performed in a direction opposite to the baseline TMS-evoked movement direction (in this case: flexion and adduction). The direction of TMS-evoked thumb movements was determined again at Post 1 as done during Pre. After a 10-min rest period, a second assessment of TMS-evoked thumb movements was repeated (Post 2). Session 2 (i.e., Paired-Pulse Measures): a subgroup of participants returned on a separate day to undergo paired-pulse TMS measures (i.e., SICI, LICI, and ICF).

Figure 2

Percentage of movements falling in the training target zone (TTZ). There was a significant increase in movements falling within the TTZ, reflecting increased UDP, from Pre to Post 1 (TTZ Delta1) which was short lived (i.e., TTZ Delta 2, Pre-Post 2) for the chronic insomnia group (CI, black bars) but not for the good sleeper group (GS, white bars). Asterisk denotes P ≤ 0.03. Data are means ± SE.

Figure 3

Corticomotor excitability, measured by motor-evoked potential (MEP) amplitude for the agonist and antagonist muscles involved in motor training. (A) Changes in the MEP amplitude recorded from the training for chronic insomnia group (CI, closed black squares) and good sleeper group (GS, open circles) for agonist and antagonist muscles. MEP amplitudes significantly increased in the CI group only. (B) The MEP Agonist Delta 1 (Pre-Post 1) was significantly greater for the CI than GS but there was no significant difference at MEP Agonist Delta 2 (Post 2-Pre). (C) The MEP Antagonist Delta 1 and Delta 2 were not significantly different between groups. Asterisks denote P ≤ 0.03. Data are means ± SE.

Figure 4

Group Differences in ICF, SICI, and LICI. The chronic insomnia group (CI, black circles) demonstrated a significant increase in intracortical facilitation (ICF), but no difference in short and long interval intracortical inhibition (SICI and LICI, respectively) relative to good sleepers (GS, white circles), supporting increased glutamatergic mechanisms. Asterisk denotes P ≤ 0.01. Data are means ± SE.