The Effects of Repetitive Transcranial Magnetic Stimulation in Healthy Human Subjects
Summary
It has been suggested that the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) are mediated through changes in cortical inhibition (CI). However, in healthy subjects the effects of rTMS on CI have been inconsistent. The aim of this study is to explore different rTMS - stimulus conditions neurophysiological and molecular mechanisms in the human motor cortex. Thirty-six healthy subjects will be randomized into three different treatment groups and receive 10 active or sham rTMS sessions at 90% of their motor threshold (MT). Cortical inhibition will be indexed pre and post treatment using short-interval intracortical inhibition (SICI), cortical silent period (CSP) and long-interval cortical inhibition (LICI).
Based on previous studies we hypothesize that:
- Hypothesis 1: rTMS will result in a greater CI (i.e., prolonged CSP, increased LICI but not SICI) compared to sham rTMS.
- Hypothesis 2: 20 Hz rTMS will result in a significantly greater CI compared to 1 Hz rTMS.
- Hypothesis 3: There will be a marked potentiation of CI following 10 rTMS treatments compared to 1 rTMS treatment.
- Hypothesis 4: There will be distinctive transcription profiles associated with increases in CI from rTMS that can be detected with whole-genome microarray analysis of peripheral leukocytes.
Description
It has been demonstrated that several neurologic and psychiatry disorders are associated with dysfunctional cortical inhibitory mechanisms and alterations in neurotrophins (biological markers involved in neuronal survival and plasticity) and that rTMS therapeutic effects are associated with changes in cortical excitability. CI produced by rTMS can be demonstrated through SICI, CSP and LICI. However it remains unclear which rTMS parameters induce the best CI. Exploring different rTMS stimulus conditions versus sham condition effects in CI of human motor cortex can be the way to identify the best rTMS therapeutic parameters. Also, evaluating the molecular effects produced by rTMS treatment on serum blood levels can help identify the mechanisms through which rTMS exerts its therapeutic effects and ultimately clarify mechanisms through which treatment effects are mediated.
This experiment intends to demonstrate the best rTMS parameters to acquire higher CI. If our hypotheses are correct, these parameters will help to obtain higher therapeutic effects, and consequently, improvement of rTMS treatments.
Study Design
Allocation: Randomized, Control: Active Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science
Conditions
Repetitive Transcranial Magnetic Stimulation
Intervention
repetitive transcranial magnetic stimulation (rTMS), repetitive transcranial magnetic stimulation (rTMS), sham repetitive transcranial magnetic stimulation (rTMS)
Location
Centre for Addiction and Mental Health
Toronto
Ontario
Canada
M5T 1R8
Status
Active, not recruiting
Source
Centre for Addiction and Mental Health
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00658307
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Evoked Potentials, Motor
The electrical response evoked in a muscle or motor nerve by electrical or magnetic stimulation. Common methods of stimulation are by transcranial electrical and TRANSCRANIAL MAGNETIC STIMULATION. It is often used for monitoring during neurosurgery.
Dna Sequence, Unstable
A region of DNA that is highly polymorphic and is prone to strand breaks, rearrangements or other MUTATIONS because of the nature of its sequence. These regions often harbor palindromic, or repetitive sequences (REPETITIVE SEQUENCES, NUCLEIC ACID). Variability in stability of the DNA sequence is seen at CHROMOSOME FRAGILE SITES.
Transcranial Magnetic Stimulation
A technique that involves the use of electrical coils on the head to generate a brief magnetic field which reaches the CEREBRAL CORTEX. It is coupled with ELECTROMYOGRAPHY response detection to assess cortical excitability by the threshold required to induce MOTOR EVOKED POTENTIALS. This method is also used for BRAIN MAPPING, to study NEUROPHYSIOLOGY, and as a substitute for ELECTROCONVULSIVE THERAPY for treating DEPRESSION. Induction of SEIZURES limits its clinical usage.
Interspersed Repetitive Sequences
Copies of transposable elements interspersed throughout the genome, some of which are still active and often referred to as "jumping genes". There are two classes of interspersed repetitive elements. Class I elements (or RETROELEMENTS - such as retrotransposons, retroviruses, LONG INTERSPERSED NUCLEOTIDE ELEMENTS and SHORT INTERSPERSED NUCLEOTIDE ELEMENTS) transpose via reverse transcription of an RNA intermediate. Class II elements (or DNA TRANSPOSABLE ELEMENTS - such as transposons, Tn elements, insertion sequence elements and mobile gene cassettes of bacterial integrons) transpose directly from one site in the DNA to another.
Ultrasonography, Doppler, Transcranial
A non-invasive technique using ultrasound for the measurement of cerebrovascular hemodynamics, particularly cerebral blood flow velocity and cerebral collateral flow. With a high-intensity, low-frequency pulse probe, the intracranial arteries may be studied transtemporally, transorbitally, or from below the foramen magnum.
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