8. MEP Dose Response Curve

MEP Dose Response Curves Protocol of the BEST Toolbox, trigger the stimulating device on trial by trial basis in a given inter-trial-interval against set of stimulation intensity conditions and presents you online results of MEPs in order to visualize the MEP shape and quality of data being collected as well as the scatter plot of the dose-response curve and a sigmoid fitted dose-response curve at the stop event or when all trials are completed. In its advanced form, Brain State- Dependent MEP Dose-Response Curve can also be configured using the parameters explained below. The flexible stimulation condition designer also facilitates versatile Paired Pulse protocols such as Short Interval Intracortical Inhibition (SICI), Long Interval Intracortical Inhibition (LICI), Short Afferent Inhibition (SAI) etc. Dependent on the Dose Function selected in the Parameters, various important results such as Inflection Point, Plateaus, Inhibition and Facilitation are also estimated from the resulting Dose-Response curve in run time and annotated on the results.

8.1. Parameters Syntax

8.1.1. Brain State

In Brain State Independent case, Inter Trial Interval controls the timing of the stimulus whereas in Brain State dependent case, real-time EEG analysis allows to track the ongoing Phase and Amplitude thresholds thereby allowing to determine specific Brain States such as mu-Rhythm Peak Phase etc. and then delivers the stimulus upon a parametric case match.

8.1.2. Input Device

Select the input device using drop down menu from previously added devices

8.1.3. Inter Trial Interval

ITI scalar, or a range in seconds e.g. 4 or [4 6] or a cell array in order to create ITI based experimental conditions e.g. {4,5,6}

8.1.4. Trials Per Condition

Various conditions can be created using ITI, Oscillation Target Phase and/or Amplitude and using the interactive Stimulation Parameters Designer. This field applies to all the created conditions and should be a scalar number e.g. 10 or 20 etc.

8.1.5. EMG Target Channels

Type the channel names as a 1xN cell array in order to get a Dose-Response curve for e.g. { ‘APBr’,’FDIr’}. Note that the channel name must resolve to the name in your streaming data. Each target channel is crossed with all the other conditions of ITI, Phase, Amplitude and stimulation conditions.

8.1.6. EMG Display Channels

Type the channel name as a 1xN cell array in order to visualize its online results e.g. { ‘APBr’}. Note that the channel name must resolve to the name in your streaming data, however Display Channels does not contributes for Threshold Measurement, these channels are merely for visualization e.g. in case when neighboring muscles are also required to be monitored.

8.1.7. EMG Extraction Period

[min max] in ms

8.1.8. EMG Display Period

[min max] in ms

8.1.9. MEP Search Window

Time window to look for the MEP P2P amplitude. [min max] in ms

8.1.10. Trials to Average

Both of the threshold methods , average certain number of trials in order to estimate the final threshold value, this parameter is specified as a scalar e.g. 10 and can be updated in run time as well.

8.1.11. Dose Function

Select the independent variable to be be treated as Dose in the Protocol. CS and ISI are useful Dose Functions while dealing with Paired-Pulse protocols.

8.1.12. Response Function

In order to facilitate Paired-Pulse Inhibition and Facilitation protocols, the Response Function has been introduced, all the TS+CS conditions (the numerator of Response Function) are given (condition number as shown in the Table) in the first field and only TS conditions (the denominator of the Response function) are given in the second field. There should be only 1 condition number in the 2nd field i.e. only 1 TS only condition, or as much condition numbers in the 2nd field as in the first field i.e. each TS+CS Condition will be balanced by its respective TS only condition.

Note: In case when there is no Response Formula such as Single Pulse Dose-Response curve, used 1 in both the fields.

For example in case when there are 4 conditions in total and first three conditions (as per the Table’s column of Condition #) are TS+CS conditions and the last one is TS only, then the first field of Response function would be [1 2 3] and the second field would be [4].

8.1.13. Real-Time Channels Montage

1xN cell array of Channel Names being streamed from the bio signal processor e.g. { ‘C3’, ‘FC1’, ‘FC5’, ‘CP1’, ‘CP5’}

8.1.14. Real-Time Channels Weights

1xN Numeric array of weights indexed w.r.t. to Channels Montage explained above e.g. 1 -0.25 -0.25 -0.25 -0.25

8.1.15. Frequency Band

Choose the respective frequency band from the dropdown (Hz).

8.1.16. Peak Frequency

Scalar Peak Frequency in Hz. In order to import it from created or successful rsEEG Measurement Protocol, select the respective rsEEG Measurement protocol from the adjacent dropdown menu.

8.1.17. Target Phase

1xN Numeric array of Phase angles in radians. This parameter also creates N experimental conditions crossed over with all the other experimental conditions. If columns in this parameter is balanced with the rows in Amplitude Threshold parameter, then balanced conditions are created otherwise these 2 parameters are also crossed over.

8.1.18. Phase Tolerance

Scalar Tolerance value in radians. Defining absolute target phase angles in order to detect a brain state is often prone to error mainly due to the resolution of data obtained after sampling rate transition. In order to overcome this digitization resolution error another parameter has to be defined such that the vicinities of the target phase shall be made clear to the detection algorithm. For an instance, while detecting a 0 radians phase, the phase vector would probably look like this [-0.001324 -0.00234 0.00243 0.004324], and since none of them are mathematically equivalent to zero therefore in order to not allow to skip such Oscillatory Peak events and to increase the accuracy of the phase detection, a tolerance value is to be provided.

8.1.19. Amplitude Threshold

Nx2 Numeric array of Amplitude Thresholds. The 2 column dimensions are minimum and maximum thresholds where as N (number of rows) creates N Amplitude Threshold conditions crossed over with all the other experimental conditions. If columns in this parameter is balanced with the rows in Target Phase parameter, then balanced conditions are created otherwise these 2 parameters are also crossed over. Units are selected from the drop-down adjacent to the parameter.

8.1.20. Amplitude Assignment Period

If the Amplitude Threshold units are percentile, then the percentile is calculated over a certain time period defined in this parameter. This parameter enables the Brain State detection algorithms to cope with the variations in amplitude of large scale oscillatory activity e.g. due to variations in background neuronal activity.

8.1.21. EEG Extraction Period

[min max] in ms

8.1.22. EEG Display Period

[min max] in ms

8.1.23. EMG Preinervation Search Window

[min max] in ms. Default is [-50 -5] i.e. 50 ms before stimulation to 5 ms before stimulation. The preinveration search window is used to measure amplitude of EMG in this duration to provide checks for quality control.

8.1.24. EMG Preinervation Amplitude

[amplitude] in uV. Default is [200] i.e. The trials having EMG amplitude of or greater than 200uV during the preinervation search window period are considered bad and rejected and replaced immediately.

This parameter can also be used to provide range of max and min [min max] e.g. [100 300] uV amplitude as user-defined range of acceptable EMG muscle activity e.g. 10-30% Maximum Voluntary Contraction (MVC) action.

8.2. Creating Conditions Using Stimulation Parameters Designer

The Target Channels and Stimulation Trigger pattern can be defined in an interactive Stimulation Parameters Designer comprising of a tabular and graphical view. Following video illustrates that how conditions can be created using the intuitive designer. Note that the example below is associated to Motor Threshold Hunting however exactly same procedure applies for the Psychometric Threshold Hunting to create Threshold conditions.

8.3. Starting the Protocol

To start this Protocol, just press the “Run” button at the bottom of the “Experiment Controller”. The measurement can be stopped, paused/unpaused. In order to check if all the parameters have been setup correctly, pressing the “Compile” button would prompt the results of compiled code whether its good to go or not.

8.4. MEP amplitude estimation procedure

MEP amplitude estimation follows procedure described in Bergmann et al, Journal of Neuroscience 2019.