/* Copyright (C) 2011 Georgia Institute of Technology This program is free software: you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation, either version 3 of the License, or (at your option) any later version. This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for more details. You should have received a copy of the GNU General Public License along with this program. If not, see <http://www.gnu.org/licenses/>. */ /* In this version, output(0) is used to control a 470 nm LED to have depolarizing effect (e.g. by activating Cheriff) and output(1) is used to control a 617 nm LED to have depolarizing effect (e.g. Jaws). This version makes use of a new concept, namely that of the PID-controller, where output is regulated based on present information (P), past infromation (I) and expected information (D) */ #include <APqrPID3.h> #include <math.h> #include <vector> /* ************ * APqrPID3 * ************ This software provides an Action Potential Cure (APqr) to correct divergent membrane potentials in excitable biological systems. The first X action potentials are logged when the software starts, after which AP correction starts from the (X+1)-st AP onwards. This correction occurs with the use of LED-controlled illumination on optogenetically modified cells. IN: *) V_cutoff Threshold potential for the detection of the beginning of an AP *) Slope_tresh Slope threshold that defines the beginning of the AP (mV/ms) *) BCL_cutoff Threshold value for the end of an AP, given as a percentage of the total APD *) lognum Number of APs that need to be logged as a reference *) Rm_blue Initial resistance for the blue LED channel *) Rm_red Initial resistance for the red LED channel *) corr_start Gives the possibility to start at a later time than the lognum+1-st AP with correcting the AP *) Blue_Vrev Apparent reversal potential of the 'blue' ChR current *) K_p Scale factor for the proportional part of the PID *) K_i Scale factor for the integral part of the PID *) K_d Scale factor for the derivative part of the PID *) length Amount of points that need to be taken into account to find the derivative (slope of the linear trend line of these points) *) PID_tresh treshold value under which the same output as before gets repeated *) min_PID value under which the lights get switched off *) reset_I_on value that indicates whether or not to reset I at RMP OUT: *) VLED1 voltage that is used to power the first LED driver that regulates the light that is shined onto the cells *) VLED2 voltage that is used to power the second LED driver that regulates the light that is shined onto the cells */ /* createRTXIPlugin ---------------- Creation of a new RTXI Plugin IN: *) None OUT: *) RTXIPlugin */ extern "C" Plugin::Object *createRTXIPlugin(void) { return new gAPqrPID3(); } static DefaultGUIModel::variable_t vars[] = { { "Vm (mV)", "Membrane potential (mV)", DefaultGUIModel::INPUT, }, { "VLED1", "Output for LED driver", DefaultGUIModel::OUTPUT, }, { "VLED2", "Output for LED driver", DefaultGUIModel::OUTPUT, }, { "iAP", "ideal AP", DefaultGUIModel::STATE, }, { "V_cutoff (mV)", "Threshold potential for the detection of the beginning of an AP, together with Slope_thresh", DefaultGUIModel::PARAMETER | DefaultGUIModel::DOUBLE, }, { "Slope_thresh (mV/ms)", "SLope threshold that defines the beginning of the AP (mV/ms)", DefaultGUIModel::PARAMETER | DefaultGUIModel::DOUBLE, }, { "BCL_cutoff (pct)", "Threshold value for the end of an AP, given as a percentage of the total APD", DefaultGUIModel::PARAMETER | DefaultGUIModel::DOUBLE, }, { "Rm_blue (MOhm)", "MOhm", DefaultGUIModel::PARAMETER | DefaultGUIModel::DOUBLE, }, { "Rm_red (MOhm)", "MOhm", DefaultGUIModel::PARAMETER | DefaultGUIModel::DOUBLE, }, { "lognum", "Number of APs that need to be logged as a reference", DefaultGUIModel::PARAMETER | DefaultGUIModel::DOUBLE, }, { "Correction start", "iAP count (index+1) when correction starts", DefaultGUIModel::PARAMETER | DefaultGUIModel::DOUBLE, }, { "Blue_Vrev", "Apparent reversal potential of the 'blue' ChR current", DefaultGUIModel::PARAMETER | DefaultGUIModel::DOUBLE, }, { "K_p", "Scale factor for the proportional part of the PID", DefaultGUIModel::PARAMETER | DefaultGUIModel::DOUBLE, }, { "K_i", "Scale factor for the integral part of the PID", DefaultGUIModel::PARAMETER | DefaultGUIModel::DOUBLE, }, { "K_d", "Scale factor for the derivative part of the PID", DefaultGUIModel::PARAMETER | DefaultGUIModel::DOUBLE, }, { "length", "Amount of points that need to be taken into account to find the derivative (slope of the linear trend line of these points)", DefaultGUIModel::PARAMETER | DefaultGUIModel::DOUBLE, }, { "PID_tresh", "treshold value under which the same output as before gets repeated", DefaultGUIModel::PARAMETER | DefaultGUIModel::DOUBLE, }, { "min_PID", "value under which the lights get switched off", DefaultGUIModel::PARAMETER | DefaultGUIModel::DOUBLE, }, { "reset_I_on", "value that indicates whetehr or not to reset I at RMP", DefaultGUIModel::PARAMETER | DefaultGUIModel::DOUBLE, }, { "Vm2 (mV)", "Membrane potential (mV)", DefaultGUIModel::STATE, }, { "P", "P term", DefaultGUIModel::STATE, }, { "I", "I term", DefaultGUIModel::STATE, }, { "D", "D term", DefaultGUIModel::STATE, }, { "PID", "PID term", DefaultGUIModel::STATE, }, { "Period (ms)", "Period (ms)", DefaultGUIModel::STATE, }, { "Time (ms)", "Time (ms)", DefaultGUIModel::STATE, }, { "APs2", "APs", DefaultGUIModel::STATE, }, { "log_ideal_on2", "log_ideal_on", DefaultGUIModel::STATE, }, { "BCL2", "BCL", DefaultGUIModel::STATE, }, { "enter2", "enter", DefaultGUIModel::STATE, }, { "act2", "0 or 1", DefaultGUIModel::STATE, }, { "count", "number", DefaultGUIModel::STATE, }, { "count2", "number", DefaultGUIModel::STATE, }, { "modulo_state", "number", DefaultGUIModel::STATE, }, }; /* num_vars -------- variable denoting the amount of variables that is displayed in the GUI */ static size_t num_vars = sizeof(vars) / sizeof(DefaultGUIModel::variable_t); /* gAPqrPID3 ------ This function constructs the actual GUI by basing itself on the Default GUI Model. It creates a module with a name, initializes the GUI, initializes the parameters, adds a refresh, and allows you to resize. IN: *) None OUT: *) None */ gAPqrPID3::gAPqrPID3(void) : DefaultGUIModel("APqrPID3", ::vars, ::num_vars) { setWhatsThis( "<p><b>APqr:</b><br>APqrPID3 </p>"); DefaultGUIModel::createGUI(vars, num_vars); initParameters(); update(INIT); refresh(); resizeMe(); } gAPqrPID3::~gAPqrPID3(void){} /* cleanup ------- The APqr software makes use of three list structures which need cleaning after a reset of parameters. The cleanup function takes care of this. IN: *) None OUT: *) None */ void gAPqrPID3::cleanup() { for(i=0;i<10000;i++){ Vm_log[i]=0; Vm_diff_log[i]=0; ideal_AP[i]=0; } } double gAPqrPID3::sumy(double arr[], int n, double length, double modulo) { double sumy = 0; // initialize sum // Iterate through all elements // and add them to sum for (int i = n-length+1 ; i < n+1; i++) sumy += arr[i % (int)modulo]; return sumy; } double gAPqrPID3::sumxy(double arr[], int n, double length, double period, double modulo) { double sumxy = 0; // initialize sum int j = 0; // Iterate through all elements // and add them to sum for (int i = n-length+1 ; i < n+1; i++) { sumxy += arr[i % (int)modulo] * (j*period); j++; } return sumxy; } double gAPqrPID3::sumx(double period, double length) { double sumx = 0; for (int i = 0; i<length; i++) sumx += i*period; return sumx; } double gAPqrPID3::sumx2(double period, double length) { double sumx2 = 0; for (int i = 0; i<length; i++) sumx2 += i*period*i*period; return sumx2; } void gAPqrPID3::execute(void) { systime = count * period; // time in milli-seconds Vm = input(0) * 1e2; // convert 10V to mV. Divided by 10 because // the amplifier produces 10-fold amplified // voltages. Multiplied by 1000 to convert // V to mV. Vm_log[count % (int)modulo] = Vm; // Logging the measured Vm in a list // where the modulo component makes // sure you keep cycling when you have // reached the maximum number in the list. // **************************** // **************************** // ** Recording the ideal AP ** // **************************** // **************************** if(count>(int)(1/period)-1 && (Vm - Vm_log[(count-(int)(1/period)) % (int)modulo]) >= slope_thresh && APs<lognum && enter == 0 && Vm > V_cutoff) { // This statement is entered whenever an upstroke is detected and the amount of // recorded APs is smaller than lognum. // The if conditions measure the following: // 1) Whether you are far enough in the recording such that you don't accidentaly // start in an ongoing AP // 2) Whether two consecutive measuring points show a large enough slope that can // be identified with an upstroke // 3) Whether less than lognum APs were recorded // 4) Whether you are currently not in an action potential // 5) Whether the mesured voltage is above a voltage treshold BCL = (APs==-1? 0: (BCL*APs + count2)/(APs+1)); // Rolling average of the basic cycle length log_ideal_on = 1; // Switches on logging the AP count2 = 0; // Resets the logging counter enter = 1; // Switches on the indicator that an AP has started APs++; // Counts the AP upstrokes that have passed } if((Vm - Vm_log[(count-(int)(1/period)) % (int)modulo]) < 0 && enter == 1) { // This statement is entered whenever the upstroke phase of an AP is over. // The if conditions measure the following: // 1) Whether two consecutive measuring points show a negative slope // 2) Whether you currently are in an ongoing AP enter = 0; // Switches off the indicator that an AP has started } if(APs<lognum && log_ideal_on == 1) { // This statement is entered whenever logging of the AP is on // The if conditions measure the following: // 1) Whether less than lognum APs were recorded // 2) Whether the AP should be logged ideal_AP[count2] = (ideal_AP[count2]*APs + Vm)/(APs+1); // Rolling average of the AP values count2++; // Increasing the logging counter } // **************************** // **************************** // ** Detecting AP upstrokes ** // **************************** // **************************** if (act == 0 && (Vm - Vm_log[(count-(int)(1/period)) % (int)modulo]) >= slope_thresh && APs >= lognum && Vm > V_cutoff) { // This statement is entered whenever an upstroke is detected after the // ideal APs have been recorded. // The if conditions measure the following: // 1) Whether currently nothing is being done or corrected // 2) Whether two consecutive measuring points show a large enough slope that can // be identified with an upstroke // 3) Whether lognum APs were already recorded before // 4) Whether the mesured voltage is above a voltage treshold count = 0; // Reset the correction counter act = 1; // Switch the correction on } // Part of the code that implements the PID if (act == 1) { iAP = ideal_AP[count]; Vm_diff_log[count] = Vm - ideal_AP[count]; if (VLED < 5 && (Vm < blue_Vrev || Vm_diff_log[count] > 0)) //this line was modified so that Int is only calculated when the output has not reached its maximum (5V) and either hyperpolarization is needed (red ch) or depolarization is needed (blue ch) and Vm is more negative than blue_Vrev. {Int = Int + Vm_diff_log[count];} num = length *(sumxy(Vm_diff_log, count, length, period, modulo)) - sumx(period, length)*sumy(Vm_diff_log, count, length, modulo); denom = length*sumx2(period, length) - sumx(period, length)*sumx(period, length); if (abs(denom) < 0.001) {slope = 10000;} else {slope = num/denom;} // Slope is measured in mV/ms P = K_p * Vm_diff_log[count]; // Term that is proportional to the instantaneous difference in voltage. I = K_i * Int; // Term that speeds up or slows down the rate of change based on the history of voltage differences. D = K_d * slope; // Term that predicts the behaviour that is about to happen and helps in stabilizing. PID_diff = PID; PID = P + I + D; PID_diff = PID_diff - PID; if (count >= corr_start-1 && abs(PID_diff) > PID_tresh){ // PID_tresh gives a value that bounds the actions of the output (applies to PID_diff). // When smaller than this value, the previous light-ouput will be repeated. // This explains the lack of an else case. if (PID < 0 && abs(PID) > min_PID && Vm < blue_Vrev) { // min_PID gives a value where you don't consider it necessary to correct anything (applies to PID). // So when the absolute value is smaller than this value, the output will be set to 0. // This is the else case. VLED = -PID * (1/Rm_blue); if (VLED > 5){VLED = 5;} output(0) = VLED; output(1) = 0; } else if (PID > 0 && abs(PID) > min_PID) { VLED = PID * (1/Rm_red); // Rm_red scales the amount of applied light for the red channel. // By lowering this value compared to Rm_blue, it is possible to counteract the smaller effect of repolarizing currents than depolarizing currents. if (VLED > 5){VLED = 5;} output(1) = VLED; output(0) = 0; } else { output(0) = 0; output(1) = 0; } } } else { output(0) = 0; output(1) = 0; } // This part of the code resets the I and D terms when the measured AP is very close to resting membrane potential (This // is taken as the value close to the end of the ideal AP) if (reset_I_on && abs(Vm - ideal_AP[int(BCL_cutoff*BCL)]) < 0.005){ idx_diff = count - prev_idx; prev_idx = count; if (idx_diff == 1){ reset_I_counter +=1; } else{ reset_I_counter = 0; } if (reset_I_counter == length){ Int = 0; reset_I_counter = 0; } } // This part of the code makes sure no output is produced in the last part of the action potential to let the cell come to rest. if (count > BCL_cutoff*BCL){ act = 0; output(0) = 0; output(1) = 0; } count++; count_r = (double)count/1000.0; // For display purposes count2_r = (double)count2/1000.0; // For display purposes } /* Update ------ This function updates the parameters of the code depending on the flag that is given to it, where each flag is associated to a button. INIT: associated to the loading of the module MODIFY: associated to the Modify button PERIOD: associated to the period linker with the "system control panel" module PAUSE: associate to the pause button when pressing on it UNPAUSE: associated to the pause button when unpressing it IN: *) flag Indicating the state of the update: INIT, MODIFY, PERIOD, PAUSE, UNPAUSE OUT: *) None */ void gAPqrPID3::update(DefaultGUIModel::update_flags_t flag) { switch (flag) { case INIT: setParameter("V_cutoff (mV)", V_cutoff); setParameter("Rm_blue (MOhm)", Rm_blue); setParameter("Rm_red (MOhm)", Rm_red); setParameter("lognum", lognum); setParameter("BCL_cutoff (pct)", BCL_cutoff); setParameter("Slope_thresh (mV/ms)", slope_thresh); setParameter("Correction start", corr_start); setParameter("Blue_Vrev", blue_Vrev); setParameter("K_p", K_p); setParameter("K_i", K_i); setParameter("K_d", K_d); setParameter("length", length); setParameter("PID_tresh", PID_tresh); setParameter("min_PID", min_PID); setParameter("reset_I_on", reset_I_on); setState("Vm2 (mV)", Vm); setState("Time (ms)", systime); setState("Period (ms)", period); setState("APs2", APs); setState("log_ideal_on2", log_ideal_on); setState("BCL2", BCL); setState("enter2", enter); setState("act2", act); setState("count", count_r); setState("count2", count2_r); setState("modulo_state", modulo); setState("iAP", iAP); setState("P", P); setState("I", I); setState("D", D); setState("PID", PID); break; case MODIFY: lognum = getParameter("lognum").toDouble(); BCL_cutoff = getParameter("BCL_cutoff (pct)").toDouble(); Rm_blue = getParameter("Rm_blue (MOhm)").toDouble(); Rm_red = getParameter("Rm_red (MOhm)").toDouble(); slope_thresh = getParameter("Slope_thresh (mV/ms)").toDouble(); V_cutoff = getParameter("V_cutoff (mV)").toDouble(); corr_start = getParameter("Correction start").toDouble(); blue_Vrev = getParameter("Blue_Vrev").toDouble(); K_p = getParameter("K_p").toDouble(); K_i = getParameter("K_i").toDouble(); K_d = getParameter("K_d").toDouble(); length = getParameter("length").toDouble(); PID_tresh = getParameter("PID_tresh").toDouble(); min_PID = getParameter("min_PID").toDouble(); reset_I_on = getParameter("reset_I_on").toDouble(); systime = 0; count = 0; APs = -1; BCL = 0; log_ideal_on = 0; enter = 0; count2 = 0; PID = 0; PID_diff = 0; Int = 0; cleanup(); break; case PERIOD: period = RT::System::getInstance()->getPeriod() * 1e-6; // time in milli-seconds modulo = (1.0/(RT::System::getInstance()->getPeriod() * 1e-6)) * 1000.0; break; case PAUSE: output(0) = 0.0; output(1) = 0.0; act = 0; systime = 0; break; case UNPAUSE: break; default: break; } } /* initParameters -------------- This function sets all values to their defaults when no external parameters are provided through the GUI interface. IN: *) None OUT: *) None */ void gAPqrPID3::initParameters() { Vm = -80; // mV Rm_blue = 150; // MOhm Rm_red = 50; // MOhm slope_thresh = 5.0; // mV corr_start = 0; blue_Vrev = -20; VLED = 0; output(0) = 0; output(1) = 0; period = RT::System::getInstance()->getPeriod() * 1e-6; // ms systime = 0; count = 0; idx_diff = 0; prev_idx = 0; reset_I_counter = 0; PID = 0; length = 10; act = 0; iAP=0; BCL = 0; count2 = 0; APs = -1; V_cutoff = -40; BCL_cutoff = 0.8; enter = 0; log_ideal_on = 0; lognum = 3; count_r = 0; count2_r = 0; modulo = (1.0/(RT::System::getInstance()->getPeriod() * 1e-6)) * 1000.0; Int = 0; num = 0; denom = 1; slope = 0; P = 0; I = 0; D = 0; K_p = 1; K_i = 0.1; K_d = 0.1; PID_diff = 0; PID = 0; PID_tresh = 0.1; min_PID = 0.2; reset_I_on = 0; }