Clinical trial NCT03309696: Regulating Homeostatic Plasticity and the Physiological Response to rTMS
Official title: Regulating Homeostatic Plasticity and the Physiological Response to rTMS
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Tinnitus
Lead sponsor: University of Arkansas
Sponsor class: OTHER
First posted: 2017-10-13
Enrollment: 10
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This prospective, experimental design includes a block randomized, blinded, sham controlled, mixed effects model with sequential assignment to treatment arms (1 or 10 Hz rTMS) and random assignment to the tDCS conditions within each arm. The order of the three experimental conditions within each arm is randomized.
Primary purpose: BASIC_SCIENCE

Brief summary: This device-study includes a pilot, physiological investigation of normal human subjects. The aim is to determine how existing non-invasive neuromodulation devices affect brain circuitry as measured by EEG recording. Currently, the application of non-invasive neuromodulation is rarely guided by detailed knowledge of how neural activity is altered in the brain circuits that are targeted for intervention. This gap in knowledge is problematic for interpreting response variability, which is common. To address this gap, the current proposal aims to combine two forms of neuromodulation sequentially, transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), to regulate homeostatic plasticity prior to rTMS delivery at different frequencies of rTMS. Homeostatic plasticity, the initial activation state of a targeted circuit, is a key determinant of whether rTMS induces long term potentiation (LTP) or long term depression (LTD) Yet, homeostatic plasticity is rarely measured or controlled in rTMS studies. We aim to control homeostatic plasticity by preconditioning the targeted circuits with tDCS prior to rTMS delivery. The protocol included an exploratory aim to examine physiological changes in patients with tinnitus but this aim was not part of the pilot physiological investigation and it could not be completed due to funding limitations.

Detailed description: Background and Rationale: The current proposal aims to combine two forms of neuromodulation, transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), to regulate homeostatic plasticity prior to rTMS delivery at two different frequencies (1Hz and 10Hz). Homeostatic plasticity, the initial activation state of a targeted circuit, is a theoretical determinant of whether rTMS induces long term potentiation (LTP) or long term depression (LTD).Yet, homeostatic plasticity is rarely measured or controlled in rTMS studies. In a physiological investigation of health subjects, we aim to control homeostatic plasticity by preconditioning the targeted circuits with tDCS prior to rTMS delivery. The justification for this study is that controlling homeostatic plasticity can reduce subject variability and the knowledge gained can be used to optimize rTMS delivery. What is needed to move the field forward is a method for combining tDCS and rTMS and for measuring neuronal responses directly which we aim to establish in this study. The pilot study project will examine the targeted effects of neuromodulation in normal subjects. The brain regions targeted for intervention include auditory areas in the temporal cortex (TC) that process sounds and functionally connected regions of the dorsolateral frontal cortex (DLFC) that mediate sensory habituation. Due to funding limitations, only the 1 Hz rTMS condition could be initiated.

Eligibility criteria: Inclusion Criteria:

* complete the informed consent process
* men and women, age: 21-65 years
* negative pregnancy test (female subjects of childbearing age must take a pregnancy test).

Exclusion Criteria:

* a personal or family history of epilepsy,
* severe head injury, aneurysm, stroke, previous cranial neurosurgery,
* sever or recurrent migraine headaches,
* metal implants in the head or neck, a pacemaker,
* pregnancy,
* medications that lower seizure threshold,

Primary outcomes:
measure: Log Transformed P100 Amplitude of TEPs From the Global Mean Field Analysis.
timeFrame: Up to 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
Study officials:
affiliation: University of Arkansas
name: Mark Mennemeier, PhD
role: PRINCIPAL_INVESTIGATOR
References: