The Effects of Immobilisation and Exercise on Homeostatic Plasticity Mechanisms in Healthy Participants
Condition: Healthy
Study type: Interventional

Summary: 
      Homeostasis is important for maintaining a stable equilibrium of e.g., blood pressure,
      hormonal release, and release of neurotransmitters. Within the healthy brain, homeostatic
      plasticity mechanisms ensure stability in synaptic plasticity that maintains cortical
      excitability within a normal physiological range, while this regulation has been shown to be
      impaired in chronic pain conditions such as low back pain. Cortical excitability can also be
      decreased and increased experimentally, using immobilisation and exercise paradigms,
      respectively, yet it is unknown if this overall change in excitability is caused by a shift
      in homeostatic plasticity regulation. Investigating if immobilisation and exercise influences
      homeostatic plasticity responses, may therefore reveal important information on the
      malleability of homeostatic plasticity mechanisms and ways to modulate them.
    

Detailed description: 
      The aim of this study is to investigate the impact of upper limb immobilisation and physical
      exercise of the hand on homeostatic plasticity in healthy individuals.

      The study will be performed as a randomised cross-over study where each participant take part
      in three sessions, separated by approximately 24 hours. During each session, the participant
      will answer questionnaires and undergo quantitative sensory testing (QST). Baseline measures
      is obtained using transcranial magnetic stimulation (TMS)-induced motor evoked potentials
      (MEPs), which is done before the induction of homeostatic plasticity using transcranial
      direct current stimulation (tDCS). MEPs are then obtained every 10 minutes for 30 minutes.
      Lastly, QST measures are obtained again.

      As no previous studies have investigated the effect of immobilisation and exercise on
      homeostatic plasticity response, a sample size calculation was estimated based on MEP
      analysis from a previous study using α of 0.05, β of 0.80, and effect size of 0.29, yielding
      22 participants. This is consistent with recent exploratory research that suggested that up
      to 28 participants would be needed. Therefore, the current study aimed at including 28
      participants with an interim analysis performed after 10-15 inclusions.

      Each participant will attend three identical experimental sessions on the same time on three
      consecutive days. Eight hours before attending the experimental sessions with immobilisation
      the participant will be fitted a splint (MANU-Hit DIGITUS POLLEX, Clinical Innovations, DK)
      to immobilise the right hand. Similarly, eight hours before attending the exercise session,
      the participant will be instructed to perform 150 ballistic finger movements with a pace of
      0.5 Hz. During the experiment, the participant will be seated comfortably with arms and hands
      at rest. Electromyography electrodes will be placed on the right first interosseous muscle to
      assess the corticomotor excitability by recording of TMS induced MEPs on the left primary
      motor cortex. A neoprene cap will then be mounted to the head, and the optimal site for TMS
      (hotspot) will be identified and marked on the cap for standardisation. The cortical
      excitability will be measured before and immediately after homeostatic plasticity induction
      (time point 0-min), and then every 10 minutes for 30 minutes.

      Homeostatic plasticity will be induced using tDCS applied to the left primary motor cortex
      for 7 minutes, followed by a break of 3 minutes and another 5 minutes of tDCS. A constant
      current of 1mA will be transmitted through the tDCS system (Starstim 32, Neuroelectrics,
      Barcelona, Spain) using two gelled electrodes placed into holes of a neoprene cap at the
      position of C3 and Fp2.

      The distribution of the data will be tested using a Shapiro-Wilk's test of normality. To
      investigate the effect of immobilisation and exercise on homeostatic plasticity, a two-way
      repeated measures analysis of variance (RM-ANOVA) will be conducted with factors Session
      (Session 1, session 2, and session 3) and Time (baseline, 0 min, 10 min, 20min, and 30 min)
      and a P value of <0.05 will be considered statistically significant. Adjustments will be made
      for multiple post-hoc comparisons using appropriate corrections.
    

Intervention name(s): Immobilisation; Exercise
Intervention type(s): Other; Other
Intervention description(s): Eight hours prior to attending the immobilisation session, a splint will be fitted to the hand of the participant and remain until the session start.; Eight hours prior to attending the exercise session, the participant will be instructed to perform 150 ballistic finger movements every hour until the session start.
Intervention model: Single Group Assignment
Intervention model description: This is a within-subject repeated measures comparisons study with one baseline session and two interventional sessions.
Masking: None (Open Label)
Primary purpose: Basic Science