Frontal and Parietal Contributions to Proprioception and Motor Skill Learning

Study Overview
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Brief Summary
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The purpose of this study is to understand how the different regions of the brain affect our sense of limbs in space (proprioception) and in turn our hand movements (motor skill learning). This information might help us one day to generate better rehabilitation protocols to help patients with movement deficits.

Detailed Description
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Moving our hands accurately, and learning new movement skills, depends on accurate sensory information. One of the sensory inputs which is crucial to make accurate movements is proprioception (sense of our limbs in space). Failure in estimating hand position results in inaccurate movement, raising the potential for accidents and injuries, but how the healthy brain carries out these functions, and how they could be strengthened in populations with sensory and motor deficits (e.g. stroke), is unknown. With greater understanding of these processes in the healthy brain, it may one day be possible to develop rehabilitation strategies that target a patient's unique mix of sensory and motor deficits. A robust way to identify whether a brain region plays a role in a behavior is to temporarily modulate its excitability in healthy people using non-invasive brain stimulation. This is commonly done in research with a short sequence of low-intensity transcranial magnetic stimulation (TMS), also known as repetitive TMS (rTMS). rTMS is used clinically to treat conditions such as depression and is considered very low risk provided the generally accepted screening criteria are met. In the research setting, this technique is widely used not only in healthy adults (as in this study) but also in children and people with concussion, stroke, Parkinson's disease, and more. In separate groups of subjects, we will use rTMS over one of several brain regions of interest before the subject In separate groups of subjects, we will use a 40-second sequence of rTMS called continuous theta burst stimulation (cTBS) over one of several brain regions of interest before the subject performs performs proprioceptive and skill learning tasks known to involve sensory and motor skill (learning). If performance of the task is affected by rTMS for a given group (relative to the sham, or control, group), it means that brain region plays some role in that type of proprioceptive or skill task.

Official Title
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Frontal and Parietal Contributions to Proprioception and Motor Skill Learning

Conditions
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Basic Science

Intervention / Treatment
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* Other: Theta burst transcranial magnetic stimulation
* Other: Sham theta burst transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Potential subjects must be between the ages of 18-45 years old and right-handed. We will only test right-handed individuals. We will only include individuals who report being free of Covid symptoms in week preceding testing. Exclusion Criteria: Current vision problems, other than needing glasses or contacts. Subjects will also be excluded if they currently suffer from frequent severe headaches, glaucoma, heart or respiratory disease, hypertension, psychiatric conditions, or learning or attention conditions. They will also be excluded for current or past: visual, hearing, or balance impairments; stroke, seizure/epilepsy (including family history), or severe head trauma; fainting; or diabetes. Subjects will be excluded for metal implants in the head other than titanium; cochlear implants; implanted neurostimulator; cardiac pacemaker; intracardiac lines; or a medication infusion device. Because TMS does not penetrate deeply into the head, we cannot test subjects whose hair does not permit contact between the TMS coil and the scalp. We will therefore exclude subjects with dreadlocks, weaves, or hair extensions. To protect the data from extraneous peripheral influences, we will also exclude subjects who have had serious injury to the bones, joints, or muscles of either hand or arm, and have not fully recovered. For the purpose of this study, fully recovered means they no longer notice any pain, weakness, or loss of sensation in the injured area, and have no mobility limitations. For the validity of our data, we will exclude subjects taking medications or drugs that are known to affect cortical excitability and possibly seizure risk in an rTMS study. These medications/drugs are (Rossi et al., 2009): imipramine, amitriptyline, doxepine, nortriptyline, maprotiline, chlorpromazine, clozapine, foscarnet, ganciclovir, ritonavir, amphetamines, cocaine, (MDMA, ecstasy), phencyclidine (PCP, angel's dust), ketamine, gamma-hydroxybutyrate (GHB), theophylline, mianserin, fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, reboxetine, venlafaxine, duloxetine, bupropion, mirtazapine, fluphenazine, pimozide, haloperidol, olanzapine, quetiapine, aripiprazole, ziprasidone, risperidone, chloroquine, mefloquine, imipenem, penicillin, ampicillin, cephalosporins, metronidazole, isoniazid, levofloxacin, cyclosporin, chlorambucil, vincristine, methotrexate, cytosine arabinoside, BCNU, lithium, anticholinergics, antihistamines, sympathomimetics. Participants will also be excluded if they have metallic, mechanical, or magnetic implants; are claustrophobic, or are unable to remain still for long periods of time; or use an intra-uterine device (IUD) whos MR compatibility has not been established. Women who are pregnant or think they might be pregnant will also be excluded, as effects of fMRI on the unborn are not known. People who have a BMI over 30 will be excluded as it may be uncomfortable or impossible to lay in the MRI scanner. Potential subjects will be invited to reschedule if they would otherwise be eligible (according to the initial screening), but the day of testing have drunk more than 3 units of alcohol or taken other recreational drugs in the 24 hour period prior to testing; have had more than 3 cups of coffee in the last hour; are sleep deprived (<4 hours sleep the previous night); or have participated in another brain stimulation experiment the same day. These are standard in the TMS literature to protect the validity of the data and keep seizure risk minimal. In addition, we will invite invite subjects to reschedule if they have any of the common Covid symptoms within the last week. If they don't believe they can meet these criteria on another date, they will be excluded. After giving their consent, participants may be excluded during or after the familiarization session if they are unable to perform the tasks or follow instructions, or if their TMS stimulation parameters cannot be reliably determined by the experimenter, or if TMS is not well tolerated.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dorsolateral prefrontal cortex (DLPFC)<br>Theta burst transcranial magnetic stimulation (cTBS) will be applied over dorsolateral prefrontal cortex (DLPFC). | Other: Theta burst transcranial magnetic stimulation<br>* Continuous theta burst TMS (cTBS) will be delivered to a location on the head. cTBS consists of 600 low-intensity TMS pulses delivered over 40 seconds in a pattern of 50 Hz triplets delivered at 5 Hz.<br>|
| Experimental: Supramarginal gyrus (SMG)<br>Theta burst transcranial magnetic stimulation (cTBS) will be applied over the supramarginal gyrus (SMG). | Other: Theta burst transcranial magnetic stimulation<br>* Continuous theta burst TMS (cTBS) will be delivered to a location on the head. cTBS consists of 600 low-intensity TMS pulses delivered over 40 seconds in a pattern of 50 Hz triplets delivered at 5 Hz.<br>|
| Sham Comparator: Sham control group<br>Sham theta burst transcranial magnetic stimulation (cTBS) will be applied over the vertex. | Other: Sham theta burst transcranial magnetic stimulation<br>* Continuous theta burst TMS (cTBS) will be delivered near the head, while an unplugged TMS coil is held at the vertex. No current will be induced in the head with this procedure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motor skill | Assessed by measuring the speed accuracy tradeoff on a maze-tracing task. Participant will grasp a robotic manipulandum and move a cursor through a maze they view in a mirror. They will be asked to trace the maze at different speed ranges so we can compute accuracy at each speed. Any change in accuracy at a given speed indicates skill learning has occurred. | 1 day | 
| Proprioception | Two-alternative forced choice task where the robot moves the participant's hand in two different positions, and the participant reports whether second position was closer or further than first position. | 1 day |