Non-invasive Cerebellar Stimulation on Motor Learning
Condition: Healthy
Study type: Interventional

Summary: 
      A crossover trial with healthy volunteers will be conducted. Six sessions will be performed
      once a week in a counterbalanced order and at least with seven days washout period to
      minimize carry-over effects. In each session, volunteers will be submitted to: fatigue and
      attention levels evaluation, cortical brain activity measures through paired pulse
      transcranial magnetic stimulation (pp-TMS), handwriting test, non-invasive cerebellar
      stimulation during serial reaction time task (SRTT) and performance perception evaluation.
    

Detailed description: 
      After given prior informed consent, volunteers will be submitted to six pseudo-randomized
      sessions using a website (randomization.com) by a non-involved researcher. At study
      beginning, volunteers will be evaluated through structured questionnaire and baseline SRTT
      will be performed 24 hours before first session. Each session, will comprise the following
      experimental sequence:

        1. Fatigue and attention levels. It will be measured through an analogue scale graded from
           0 to 10, where 0 means lower fatigue or attention levels and 10, the higher fatigue or
           attention levels.

        2. Short intracortical inhibition (SICI) and intracortical facilitation (ICF): it will be
           evaluated through pp-TMS paradigms (Neurosoft, Russia). Initially, rest motor threshold
           (RMT) will be determined by finding the lowest stimulator output that elicit motor
           evoked potential (MEP) around 50 μV (TMS Motor Threshold Assessment Tool -MTAT 2.0 -
           USA). For RMT measure, a figure-eight coil connected to the magnetic stimulator held
           manually at 45 degrees from the midline, will be placed over the right primary motor
           cortex (C4 - 10/20 System). Subthreshold conditioning stimuli (80% of RMT) and
           suprathreshold test stimuli (120% of RMT) will be delivered at an interstimulus interval
           (ISI) of 2 milliseconds for SICI and 10 milliseconds for ICF. Ten stimuli will be
           applied at each condition (unconditioned pulse and pairs of stimuli with ISI of 2 and 10
           milliseconds). Stimuli order delivery will be pseudo-randomized and SICI and ICF will be
           expressed as conditioned stimulus percentage regarding unconditioned stimulus.

        3. Handwriting test: volunteers will be instructed to write six words with digital pen
           using the non-dominant hand on a tablet provided with analysis software system
           (MovAlyzer, EUA). The task will be performed spontaneously, without any instruction bias
           during writing activity. Each session has different word sequences but the difficulty
           level will be maintained (six words, two of them with 4, 6 and 8 letters).

        4. Non-invasive cerebellar stimulation + Serial Reaction Time Task: Cerebellar stimulation
           will be applied during SRTT (online acquisition).

           ctDCS - Electrical current will be delivered through a DC stimulator (NeuroConn Plus,
           Germany) using a pair of saline-soaked sponge electrodes (surface 25cm² and 35cm²). The
           active electrode (anode or cathode) will be placed over the left cerebellar area (3 cm
           lateral to the inion - left cerebellar hemisphere) and the reference, over the right arm
           with current intensity of 2mA, fade in and fade out of 10 seconds, during 20 minutes.
           Sham tDCS has been used in several studies to evaluate active tDCS effects. Sham ctDCS
           will be applied using the same electrodes placement and parameter settings of cathodal
           ctDCS however, stimulation will last only 30 seconds but volunteers will be with
           electrodes montage for 20 minutes. Because the device will be automatically turned off
           without volunteer's perception, early sensations (mild to moderate tingling) on
           stimulation site will be experienced without inducing any modulatory effects. Moreover,
           after each ctDCS session, an adverse effects questionnaire will be applied.

           c-rTMS - Initially, the higher cortical representation area (hotspot) of first dorsal
           interosseous (FDI) muscle will be determined through a figure-eight coil connected to
           the magnetic stimulator (Rapid², Magstim, UK) held manually and positioned on the scalp
           (C4 - 10/20 System) at an angle of 45 degrees from the midline pointed to the target
           muscle (FDI). Thereafter, RMT will be measure. Volunteer will be positioned in front of
           a computer screen in order to perform SRTT during stimulation. The coil will be placed
           over left cerebellar hemisphere (3 cm lateral to the inion) tangentially to the scalp
           and pointing upwards. rTMS protocols was based on previous studies and were adjusted to
           full-fit safety recommendations and also to be able to realize SRTT simultaneously
           (online acquisition). Low frequency protocol: 1Hz, 110% RMT, 1000 stimuli (1 train).
           High frequency protocol: 10Hz, 110% RMT, 33 trains, 50 stimuli per train, intertrain
           interval of 25 seconds, 1650 stimuli. Sham c-rTMS will be performed with low frequency
           protocol using two coils. The first one - connected to the stimulator - will be
           positioned on a coil support close to the volunteer but not visible. Therefore,
           characteristic stimulation noises will be audible. The second - disconnected to the
           stimulator - will be placed over left cerebellar hemisphere. After each c-rTMS session,
           presence of adverse effects will be computed.

           Serial Reaction Time Task (SRTT): it will be performed through software with visual
           stimuli presented on a computer screen in four different positions. Volunteer must
           press, with the non-dominant hand, a corresponding key with predetermined fingers as
           soon as possible when a highlighted star appears on the screen. The test comprises eight
           blocks with 120 trials each. Implicit motor learning is measured by performance changes
           between the blocks 5, 6 and 7.

        5. Short intracortical inhibition (SICI) and intracortical facilitation (ICF): using the
           same RTM as before.

        6. Handwriting test.

        7. Fatigue and attention levels.

        8. Performance perception evaluation: in order to correlate stimulation type to the
           conscious improvement on motor task performance (SRTT and handwriting test) will be
           asked in the end of each session if the volunteer considers that his motor performance
           was better, worse or the same as before.
    

Intervention name(s): tDCS; tDCS; tDCS; rTMS; rTMS; rTMS; pp-TMS assessment
Intervention type(s): Device; Device; Device; Device; Device; Device; Device
Intervention description(s): Current will be applied by a DC stimulator (NeuroConn Plus, Germany).The active electrode (anode: 5x5 cm²) will be placed over the left cerebellar hemisphere (3 cm lateral to the inion) and the reference (5x7 cm²), over the right arm with current intensity of 2mA, fade in and fade out of 10 seconds, during 20 minutes.; Current will be applied by a DC stimulator (NeuroConn Plus, Germany). The active electrode (cathode: 5x5 cm²) will be placed over the left cerebellar hemisphere (3 cm lateral to the inion) and the reference (5x7 cm²), over the right arm with current intensity of 2mA, fade in and fade out of 10 seconds, during 20 minutes.; Sham ctDCS will be applied using the same electrodes placement and parameter settings of cathodal ctDCS. However, stimulation will last only 30 seconds but volunteers will be with electrodes montage for 20 minutes.; High frequency c-rTMS will be applied through a figure-eight coil connected to a magnetic stimulator (Rapid², Magstim, UK) placed over the left cerebellar hemisphere (3 cm lateral to the inion), tangentially to the scalp and pointing upwards. Protocol: 10Hz, 110% RMT, 33 trains, 50 stimuli per train, intertrain interval of 25 seconds, 1650 stimuli.; Low frequency c-rTMS will be applied through a figure-eight coil connected to a magnetic stimulator (Rapid², Magstim, UK) placed over the left cerebellar hemisphere (3 cm lateral to the inion), tangentially to the scalp and pointing upwards. Protocol: 1Hz, 110% RMT, 1000 stimuli (1 train).; Sham c-rTMS will be performed with low frequency protocol using two coils. The first one - connected to the stimulator (Rapid², Magstim, UK) - will be positioned on a coil support close to the volunteer but not visible. Therefore, characteristic stimulation noises will be audible. The second - disconnected to the stimulator - will be placed over left cerebellar hemisphere.; SICI and ICF will be evaluated through pp-TMS. Subthreshold conditioning stimuli (80% of RMT) and suprathreshold test stimuli (120% of RMT) will be delivered at 2 milliseconds ISI, in order to determine SICI. ICF will be evaluated by MEP average at an ISI of 10 milliseconds. Ten stimuli will be applied at each condition (unconditioned pulse and pairs of stimuli with ISI of 2 and 10 milliseconds). Stimuli order delivery will be pseudo-randomized and SICI and ICF will be expressed as conditioned stimulus percentage regarding an unconditioned stimulus.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Cerebellum; Transcranial Direct Current Stimulation; Repetitive Transcranial Magnetic Stimulation; Motor Learning; Serial Reaction Time Task; HandwritingTask