Motor Plasticity Enhancement of Spaced iTBS Trains: a Randomized, Placebo-controlled, Crossover Trial of D-cycloserine.

REB21-0863

Repetitive transcranial magnetic stimulation (rTMS) is a modality for probing and altering brain function in humans non-invasively. The technology relies on the principles of electromagnetic induction, whereby magnetic fields have an associated electrical field. By intersecting two magnetic fields safely generated outside the head, one can induce a focal electrical current where the magnetic fields intersect in the brain, and this can depolarize cell membranes and impact brain activity. A well investigated phenomenon in neuroscience is the principle of long term potentiation (LTP), and its converse long term depression (LTD), referring to the ability of neurons to increase or decrease their connection strength in an activity dependent manner. They do this through modifications to their electrochemical junctions, the synapses. We have previously used the motor system as a model system to study the impact D-Cycloserine, an NMDA receptor partial agonist, on synaptic plasticity after TMS. Conventional therapeutic TMS is delivered once daily, however it is increasingly being delivered multiple times per day in an effort to speed treatment effects. It is unclear how adjunctive agents would impact these repeated stimulation designs. Research Question: Does the N-methyl-D-aspartate receptor partial agonist D-Cycloserine stabilize motor plasticity across multiple daily sessions of TMS?

2021-08-18

2021-10-06

2022-02-23

Completed

Early phase I

20

Inclusion Criteria: 1. Healthy (absence of chronic medical conditions) individuals 2. Aged 18-65. The lower limit is justified by the absence of safety studies involving DCS in pediatric studies, and the upper limit is justified by the increasing prevalence of chronic illness. Exclusion Criteria: 1. Allergy to cycloserine 2. Are currently pregnant, breast feeding or plan to become pregnant 3. Have an alcohol or substance use disorder within the last 3 months 4. Current psychiatric concerns 5. are at a significant risk of harm to themselves or others 6. Have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of epilepsy, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than or equal to 5 minutes 7. Have concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump 8. Have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed 9. Conditions that may impair the ability to metabolize cycloserine including, but not limited to current Renal or Liver Disease. 10. Inability to refrain from alcohol use for 24 hours prior to each session and following each session. 11. Use of isoniazid or ethionamide 12. Are currently (or in the last 4 weeks) using any benzodiazepine, cyclopyrrolone, gabapentin/pregabalin or anticonvulsant due to the potential to limit rTMS efficacy

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2023-09-07