fMRI Guided TMS Enhancement of Associative Memory Networks

Study Overview
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Brief Summary
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This is a randomized, single-blinded, controlled phase 1 study to demonstrate feasibility and explore the neurophysiologic and clinical effects of repetitive transcranial magnetic stimulation (TMS) interventions in epilepsy patients and healthy controls. The inclusion of a control group will be used to see whether epilepsy patients, who suffer from a higher degree of comorbid memory difficulty presumably from entorhinal-hippocampal dysfunction, can benefit from a TMS intervention can benefit as much as a healthy matched population. Investigators will also be looking at functional connectivity between the hippocampus and cortical regions

Official Title
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A Randomized Controlled Pilot Study of TMS Enhancement of Associative Memory Networks in Healthy Subjects and Epilepsy Patients

Conditions
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Epilepsy

Intervention / Treatment
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* Diagnostic Test: MagStim RapidStim2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fluent in English Right-handed Score at least 26 out of 30 on the Montreal Cognitive Assessment (MOCA). Healthy subjects will be matched to age, handedness, and education compared to epilepsy subjects. Must be able to provide informed consent. Exclusion Criteria: Any history of a neurological disorder Chronic or progressive medical condition Any history of severe traumatic brain injury or skull defect Metal or devices in the head, including neurostimulators of metal foreign bodies Any other implanted metal device, including pacemaker, spinal cord stimulator, VNS. Any other ferromagnetic substance in the body (including tattoos, dental prosthetics, etc). Taking a medication which may lower the seizure threshold within the 4 weeks prior to the start of the study, including use of neuroleptic (esp. clozapine), antibiotic (penicillin, cephalosporins), and bronchodilating medications. Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Healthy Subjects<br> | Diagnostic Test: MagStim RapidStim2<br>* Repetitive transcranial magnetic stimulation (TMS)<br>|
| Experimental: Temporal Lobe Epilepsy Patients<br> | Diagnostic Test: MagStim RapidStim2<br>* Repetitive transcranial magnetic stimulation (TMS)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Face-Object Pair Association Task Score during Left Lateral Parietal Site Stimulation | A face-object pair association task will be administered before and after rTMS treatment at each treatment session. This measure is evaluating the mean change in the task score from immediately before rTMS is applied to the left lateral parietal site to immediately after treatment. | Immediately before Left Lateral Parietal Site Stimulation, Immediately after Left Lateral Parietal Site Stimulation (20 minute procedure; Up to Week 6) | 
| Mean Change in Face-Object Pair Association Task Score during Motor Cortex Stimulation | A face-object pair association task will be administered before and after rTMS treatment at each treatment session. This measure is evaluating the mean change in the task score from immediately before rTMS is applied to the motor cortex to immediately after treatment. | Immediately before Motor Cortex Stimulation, Immediately after Motor Cortex Stimulation (20 minute procedure; Up to Week 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fMRI-based Functional Connectivity between Hippocampus and Cortical Regions | Changes in hippocampal-cortical functional connectivity will be identified using voxel-wise paired T-tests. The change will be measured between baseline assessment and resting state fMRI assessment following rTMS. | Baseline, Week 6 | 
| Mean Change in Word-Pair Association Task Score during Left Lateral Parietal Site Stimulation | A word-pair association task will be administered before and after rTMS treatment at each treatment session. This measure is evaluating the mean change in the task score from immediately before rTMS is applied to the left lateral parietal site to immediately after treatment. | Immediately before Left Lateral Parietal Site Stimulation, Immediately after Left Lateral Parietal Site Stimulation (20 minute procedure; Up to Week 6) | 
| Mean Change in Word-Pair Association Task Score during Motor Cortex Stimulation | A word-pair association task will be administered before and after rTMS treatment at each treatment session. This measure is evaluating the mean change in the task score from immediately before rTMS is applied to the motor cortex to immediately after treatment. | Immediately before Motor Cortex Stimulation, Immediately after Motor Cortex Stimulation (20 minute procedure; Up to Week 6) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cognitive dysfunction, memory loss, non-invasive transcranial magnetic stimulation (TMS), rTMS, Magstim Rapid2