A programmable stimulator for physiological applications" H. G. Goovaerts, G. Koning and H. Schneider Department of Medical Physics, Faculty of Medicine, Free University, Van der Boechorststraat 7, AmSterdam, the Netherlands

A b s t r a c t - - The design of a computer controllable stimulator for use in the field of electrophysiology and neurophysiology is described. However, the unit is a self-supporting special timing device. Some preprogrammed types of stimulation available are: a double pulse, a train of N pulses and a stepwise variation of time interval. The unit is triggerable on physiological signals. Triggering is also possible for each interval timing. The pulses are available on three different isolated transformer-coupled current sources, supplied by a r.f. carrier. The defvered pulses are current stabilised and adjustable between O. 1 and 99 mA. The interval timing is adjustable between O. 1 ms and 9999 ms. The pulse duration may be varied between O" I ms and 9 9 . 9 ms. A l l parameters are set by means of thumb- wheel switches. K e y w o r d s - - S t i m u l a t o r , computer control

Introduction FOR THE analysis of biological systems with the technique of input-output relationships, it is necessary that the applied input signals are accurately dimensioned. In the field of electrophysiology, the input signals are generally rectangular electrical current pulses applied to the subject of study, which can be a nerve, a skeletal muscle or the heart muscle. For this purpose a stimulator has to be available to deliver these stimuluses. Although a stimulator can be used

in the whole field of electrophysiology, the stimulator presented here was designed for the investigation of the electrophysiology of the heart. The reaction of the heart to a stimulation programme can provide information about the electrical behaviour of the heart. Pulses with a fixed repetition frequency alSplied to the atria or ventricles can give an impression of the highest frequency to which the heart can respond, thus giving the frequency characteristics of the atria or ventricles. If a stepwise frequency change is applied to one of the v

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"First received 12th July and in final form 23rd October 1973

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atria, and the PR interval in the electrocardiogram is the refractory period of the heart (VANDAM et aI., measured as a function of time, the adaptation time 1956). If one pulse with a fixed delay after the constant of the A - V n o d e can be measured R wave is applied to the myocardium, the relation (HEETRAAR et al., 1973). Also a random rhythm between pulse amplitude and duration can be applied to the atria can describe the adaptation time measured as a strength-duration curve (ScI~NEIDER, constant of the A-V node. 1964). This strength-duration curve can be used to One pulse applied with a delay after the R wave characterise a physiological system having a threshold gives an impression of the excitability of the heart as [TROELSTA, (1969) stimulation; KONING (1972), a function of the delay and also gives a measure of defibrillation]. SN 7495 112 SN7400

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A double pulse consisting of two short subthreshold rectangular pulses applied to a nerve (BROMM and FRANKENHAEUS~R,1968) or to the heart (ScrINE~DER, 1966) muscle also can describe a system with a threshold. On this basis of possible applications, a design was started for a universally applicable stimulator. This stimulator should have a basic standard programme for realisation of at least the above modes of stimulation. It should also be programmable by a computer to realise more complex stimulation programmes. The setup is a digital one, resulting from the requirements of computer controllability, reliability and accuracy. This digital set up offers the possibility of extending the system, if necessary, until it meets the requirements of a specific research problem. If no computer control is needed, the stimulator's internal program still offers a variety of possibilities.

Description of the system The configuration of the system is given in Fig. 1. There are three interval pulse-width arrangements that may be controlled from the interval program as well as by the interface. The system block N is the preset counter, which makes it possible to switch after a certain number N cycles (01 + zl) to the combination (02 + T2) - (0a + ra). The computer input to the interface is enabled by the program. In Fig. 2, the most significant timing possibilities are given. In the recurrent mode, a train of N pulses will be delivered with timing (01 + r l ) by current source 1, and they are followed by pulses from current source 2 and 3 having a timing of (02 +r2) and (0a + ra), respectively. There is also a possibility of inserting the timing (02 + z2) and (03 + z3) in that of (01 + r l ) in such a way that during (02 + 7 2 ) (0a + r3) the timing of (01 + zl) will be inhibited. The return loop AuB can be disconnected automatically after N cycles of (01 + zl), so creating a change in interval timing similar to a step function. 114

By adding the current source 2 and 3, the possibility of double pulse stimulation is accomplished. In this case, 01 may be used as a delay time when the triggered mode is used. The time elapsed between the stimulus and the system's response can be measured on a counter incorporated in the stimulator.

Timing The basic unit of the stimulator is a decade counter with a presettable number of counts. The logic diagram for one decimal figure is given in Fig. 3. The complement of the binary-codeddecimal number represented by the 4 bit states is continuously compared with the terminals of the shift register containing the computer information, and the preset number on the thumbwheel switches. If, and only if, computer information is between the limits specified by the setting of the thumbwheel switches, the counter will count to the number given by the shift register. If the 4 bit states of the counter equal the 4 bits of the shift register, the input gate will be closed and will stop the counter. If the computer information has a value less than the preset lower limit, it will be rejected because of the closed gate G2. The same applies for computer information having a value of more than the preset upper limit. In this case, the counter will be stopped as soon as its contents reach the value of the preset upper limit. It is now possible to control the timing of the stimulator within certain specified margins by the computer.

Trigger system As mentioned in the preceding section, it is desirable to have at one's disposal the possibility of triggering for example from the e.c.g., to stimulate in a certain phase of the heart cycle. Fig. 4 shows the block diagram of the trigger circuit. The trigger signal is fed into an isolation

Medical and Biological Engineering

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amplifier and then passes through a gain controlled amplifier. The gain factor of this amplifier is controlled by the amplitude of the signal, which is detected in network D. In this manner, there will occur a reduction in amplitude variation of the input signal. Next the amplitude-stabilised signal is fed into a bandpass filter tuned to the most significant frequency component of the triggering signal. The output of this filter is discriminated at a certain adjustable level. A crossing of this level will result in

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Medical

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January

1975

lated in order to conduct each atrial activation to the ventricles. This has been done statically and dynamically with a stepwise change in the atrial stimulus interval. The results of this study will be used t o evaluate a pseudo-random stimulus pattern, from which each atrial stimulus will be conducted to the ventricles. A stepwise decrease in the atrial stimulus interval will result in an exponential increase of the PR interval in the e.c.g. (HEETHAAR,1973) (Fig. 7). Also it can be seen that for this change in atrial interval from 400 to 180 ms the A-V node conducts each atrial activation. The second study concerns the reaction of the ventricles to double pulse stimulation. This technique gives an impression about the time constants active in the heart stlmulation (ScHNHDER, 1966). The results of two experiments on an isolated rabbit heart perfused according to Langendorff are presented in Fig. 8. It can be seen that two subthreshold stimuli can provoke an activation of the ventricles, if the interval between those two pulses is in the order of 50#s. From this it can be concluded that the addition principle is valid for artificial heart stimulation. The intersection point of the curve with the ordinate represents the stimulation threshold for 12 while the intersection with the abcissa represents the threshold for I1. It will be clear, then, that an adequate reaction to a stimulus above threshold only will occur for values of 11-12 that are positioned on the upper and right

By using this carrier method, it is possible to transfer various pulse widths from 10 #s up to d.c., as any pulse can be imagined to be built from a train of short pulses having a constant duration. For these pulses it is possible to design a suitable transformer having very small parasitic capacitances. Fig. 5 shows the circuit diagram of the current source. The amplitudes of the current sources are adjustable from 0.1 to 9"9 mA in steps of 0' 1 mA and from 1 to 99 mA in steps of 1 mA. These values are also set by means of thumbwheel switches, and they may be set by the computer. The accuracy of the delivered pulse amplitude is within 5~o of the setting. The binary words presented by the thumbwheel switches or computer are d-a converted. The derived voltage is switched into a transformer. On the secondary side, this switched signal is rectified and will be available as a current pulse after feeding it through a current stabilising network. Fig. 6 gives the relationship between the setting of the binary-coded-decimal number and the actually presented current. Stabilisation is guaranteed over a load impedance in the range of 0-1 k~. Results The stimulator was used for two studies, concerning the electrophysiological behaviour of the heart, perfused according to Langendorff. The first study applies to the conduction properties of the A-V node. The purpose of this study is to test at which interval limits the atria can be stimu-

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