Tinnitus
Conditions
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.
Interventions
DEVICEsham tDCS and sham rTMS
Both combinations of tDCS and rTMS in this intervention are sham.
DEVICEsham tDCS and active rTMS
tDCS in this intervention is sham and rTMS is active
DEVICEactive tDCS and active rTMS
Both combinations of tDCS and rTMS in this intervention are active
Sponsors
University of Arkansas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
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.
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
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,
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Log Transformed P100 Amplitude of TEPs From the Global Mean Field Analysis. | Up to 8 weeks | TEPs refer to TMS-evoked EEG potentials. The P100 amplitude of TEPs is one means of assessing cortical excitability. The P100 amplitude has been shown to be a reliable metric in studies of healthy subjects. The P100 amplitude is used in this study to assess the excitation state of two regions of interest (ROIs), one in the TC and one in the DLPFC, at each period of TEP recording (i.e., Baseline, Post tDCS, Post rTMS, and 20 minute delay). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| tDCS and 1 Hz rTMS Delivered Over TC Baseline characteristics for participants assigned to the arm that received tDCS and 1Hz rTMS over the temporal cortex. | 5 |
| tDCS and 1 Hz rTMS Delivered Over DLPF Baseline characteristics for participants assigned to the arm that received tDCS and 1Hz rTMS over the dorsolateral frontal cortex. | 5 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Analysis of TEP data could not be completed | 0 | 5 | 0 | 0 |
Baseline characteristics
| Characteristic | tDCS and 1 Hz rTMS Delivered Over DLPF | Total | tDCS and 1 Hz rTMS Delivered Over TC |
|---|---|---|---|
| Age, Continuous | 32 years STANDARD_DEVIATION 15.14 | 33.9 years STANDARD_DEVIATION 14.16 | 35.8 years STANDARD_DEVIATION 16.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 9 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Mean baseline P100 amplitude of the GMFA | — | 1.29 µV STANDARD_DEVIATION 0.47 | 1.29 µV STANDARD_DEVIATION 0.47 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 7 Participants | 5 Participants |
| Sex: Female, Male Female | 4 Participants | 8 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 1 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Log Transformed P100 Amplitude of TEPs From the Global Mean Field Analysis.
TEPs refer to TMS-evoked EEG potentials. The P100 amplitude of TEPs is one means of assessing cortical excitability. The P100 amplitude has been shown to be a reliable metric in studies of healthy subjects. The P100 amplitude is used in this study to assess the excitation state of two regions of interest (ROIs), one in the TC and one in the DLPFC, at each period of TEP recording (i.e., Baseline, Post tDCS, Post rTMS, and 20 minute delay).
Time frame: Up to 8 weeks
Population: The analyses population is 5 subjects who were assigned to the arm tDCS and 1 Hz rTMS over the temporal cortex. The group titles reflect sequences of sham and active tDCS and rTMS conditions used to create contrasts for data analysis. Outcome measures are not reported for the DLPF arm because, due to insufficient resources and the required personnel needed to perform the extensive data cleaning and pipeline analysis, no P100 amplitude data can be reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham tDCS Preconditioning | Log Transformed P100 Amplitude of TEPs From the Global Mean Field Analysis. | 1.85 log µV | Standard Deviation 0.71 |
| Active tDCS Preconditioning | Log Transformed P100 Amplitude of TEPs From the Global Mean Field Analysis. | 1.26 log µV | Standard Deviation 0.33 |
| Sham tDCS Preconditioning of Sham rTMS | Log Transformed P100 Amplitude of TEPs From the Global Mean Field Analysis. | 1.59 log µV | Standard Deviation 0.82 |
| Sham tDCS Preconditioning of Active rTMS | Log Transformed P100 Amplitude of TEPs From the Global Mean Field Analysis. | 1.30 log µV | Standard Deviation 0.58 |
| Active tDCS Preconditioning of Active rTMS | Log Transformed P100 Amplitude of TEPs From the Global Mean Field Analysis. | 1.11 log µV | Standard Deviation 0.48 |
Comparison: Examines the effect of tDCS preconditioning on P100 amplitudes. The effect size for this comparison was .33 (Cohen's).p-value: 0.055Mixed Models Analysis
Comparison: Examines the effect of rTMS on the P100 amplitude. The calculated effect size is .35 (Cohen's).p-value: 0.0418Mixed Models Analysis
Comparison: Examines the additive effect of tDCS preconditioning on the P100 amplitude after rTMS. The effect size for this comparison was 0.14.p-value: 0.4Mixed Models Analysis
Comparison: Examines the combined effect of tDCS and rTMS on the P100 amplitude. The effect size for this comparison was .29 (Cohen's).p-value: 0.086Mixed Models Analysis