Abstract:
Neural Gastric Electrical Stimulation (NGES) is a new method for invoking gastric contractions under microprocessor control. However, optimization of this technique using feedback mechanisms to minimize power consumption and maximize effectiveness has been lacking. An apparatus and method are provided for inducing controlled gastro paresis. The apparatus comprises a contraction sensor, a stomach contraction generator, and a controller. The contraction sensor is responsive to circumferential contractions of the stomach, and outputs a signal indicative of a circumferential contraction. The stomach contraction generator induces a circumferential contraction upon receipt of an electrical signal from the controller. The controller sends the electrical signal to the generator upon receipt of the output signal from the sensor. The method comprises the steps of sensing a circumferential contraction of the stomach, and invoking a circumferential contraction of the stomach in response to sensing the circumferential contraction.

Description:
TECHNICAL FIELD 
       [0001]    The apparatus and method relate to gastro-intestinal stimulation. 
       BACKGROUND 
       [0002]    Feedback Controlled Gastric Electrical Stimulation (GES) has been used as a method of inducing symptoms of gastro paresis for the treatment of obesity. By producing retrograde peristalsis in the stomach, gastric emptying of the stomach can be delayed, leading to earlier feelings of satiety, a reduced appetite, and less food consumption. In US Patent Application Serial No. 20050149142 by Starkebaum, gastric stimulation is provided in a patient in response to sensed stomach activity. 
         [0003]    There is a need for more efficient and less invasive ways of inducing symptoms of gastro paresis in a patient. There is also a need for the optimization of GES using feedback mechanisms to minimize power consumption and maximize effectiveness. The information disclosed in this document provides a unique apparatus and method that meets these needs. 
       SUMMARY 
       [0004]    An apparatus is provided comprising a contraction sensor, a contraction generator, and a controller. The contraction sensor is located on a portion of the gastro-intestinal tract such as the stomach and is responsive to circumferential contractions of the portion of the gastro-intestinal tract. The contraction sensor has as output a signal indicative of a circumferential contraction of the portion of the gastro-intestinal tract. The contraction generator may for example be located closer to the pylorus than the contraction sensor. The contraction generator induces a circumferential contraction upon receipt of an electrical signal. The controller has, as at least one input, the output from the contraction sensor, and is configured to output an electrical signal to the contraction generator. The electrical signal is outputted upon receipt of output from the contraction sensor indicative of a contraction. 
         [0005]    A method of controlled gastro paresis is provided, comprising the steps of sensing a circumferential contraction of a portion of the gastro-intestinal tract such as the stomach, and invoking a circumferential contraction of the portion of the gastro-intestinal tract in response to sensing the circumferential contraction. The sensed circumferential contraction is sensed at a first location on the portion of the gastro-intestinal tract. The invoked circumferential contraction is invoked at a second location on the portion of the gastro-intestinal tract. In the case of the portion of the gastro-intestinal tract being the stomach, the second location may be located closer to the pylorus than the first location. 
     
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         [0006]    Embodiments will now be described with reference to the figures, in which like reference characters denote like elements, by way of example, and in which: 
           [0007]      FIG. 1  is side elevation view, partially in section, of a feedback controlled gastric stimulator positioned in the stomach; 
           [0008]      FIG. 2  shows a retrograde stimulation pattern; 
           [0009]      FIG. 3A  shows a control diagram of a feedback controlled gastric stimulator that senses circumferential contractions using a force transducer; 
           [0010]      FIG. 3B  shows a control diagram of a feedback controlled gastric stimulator that senses circumferential contractions using impedance; 
           [0011]      FIG. 4  shows a theoretical model of tissue impedance; 
           [0012]      FIG. 5  shows a circuit diagram for the synchronous demodulation of the current used with the gastric stimulator of  FIG. 1 ; 
           [0013]      FIGS. 6A and 6B  are graphs created with data from force transducers used as part of a feedback controlled gastric stimulator; 
           [0014]      FIGS. 7A and 7B  are graphs that show signs of induced gastro paresis, the graphs created with data from force transducers used as part of a feedback controlled gastric stimulator; 
           [0015]      FIG. 8  is a graph that shows a search for the optimal impedance interrogation frequency; 
           [0016]      FIGS. 9A-9C  are graphs that show the correlation between the force transducers and the impedance sensor in a feedback controlled gastric stimulator; 
           [0017]      FIGS. 10A-10C  are graphs that show signs of induced gastro paresis, the graphs showing correlation between the force transducers and the impedance sensor in a feedback controlled gastric stimulator; 
           [0018]      FIG. 11  shows a method of sensing a circumferential contraction and invoking a retrograde contraction; 
           [0019]      FIG. 12  shows a method of sensing a contraction, invoking a retrograde contraction, and observing a refractory period before repeating; 
           [0020]      FIG. 13  shows a method of detecting a circumferential contraction using the impedance along a circumference of the stomach wall; and 
           [0021]      FIG. 14  shows a method of detecting a circumferential contraction using the force of deformation of the stomach wall. 
       
    
    
     DETAILED DESCRIPTION 
       [0022]    Neural Gastric Electric Stimulation (NGES) is a type of GES that generates multi-channel high energy, high frequency waveforms that can directly invoke contractions which can move gastric content in a controlled fashion depending on the synchronization between the stimulating channels. NGES overrides any spontaneously-existing electromechanical events and does not entrain the intrinsic gastric slow waves. By stimulating the local network of cholinergic neurotransmitters, repeated local contractions can be produced. This stimulation technique has been successful in accelerating gastric emptying of both liquids and solids and in producing strong, externally-controlled, retrograde contractions. 
       Obesity and Gastric Motility 
       [0023]    The possibility to produce retrograde contractions in the stomach using GES is of particular interest for the treatment of obesity, which is considered as one of the most pressing health problems of modern society. The prevalence of obesity has increased significantly in the period of 1988-1994 and is still growing. Various disorders and conditions have been related to obesity, many of which are life-threatening. GES is a promising technique to treat obesity that could provide reliable long term results without suffering from the side effects associated with pharmacotherapy or from the postoperative complications related to bariatric surgery. Invoked and appropriately controlled retrograde peristalsis could be an important avenue for delaying gastric emptying and thus indirectly controlling satiety and food intake. Since NGES is the only method that can invoke retrograde contractions, it could be regarded as the GES method of choice for the treatment of obesity. However, this technique is energy-demanding, and if utilized in an open-loop setup could pose difficult, if not impossible long-term requirements for a multi-channel programmable implant. Moreover, recent chronic studies on experimental animals indicated that although the method was effective in reducing food intake, frequently invoked contractions in an open-loop system may lead to tissue accommodation resulting in NGES losing its ability to invoke contractility using the same amplitude of the stimulating voltage. Therefore, optimization of the invoked contractile patterns using feedback control is an important avenue to increase the effectiveness and the applicability of NGES. 
         [0024]    Referring to  FIG. 1 , a feedback controlled gastric stimulator  10  is illustrated comprising a contraction sensor  12 , a stomach contraction generator  14 , and a controller  16 . Contraction sensor  12  is located on a stomach  18  and is responsive to a circumferential contraction of stomach  18 . Contraction sensor  12  has as output a signal indicative of a circumferential contraction of the stomach. Stomach  18  has a gastric axis  28 , a fundus  36 , an antrum  38 , and a pylorus  40 . Gastric axis  28  defines the center of an infinite number of imaginary circumferences of stomach  18  running from an esophagus  42  to a duodenum  44 . Stomach contraction generator  14  is located on stomach  18  closer to pylorus  40  than contraction sensor  12 . Contraction generator  14  is located to induce a circumferential contraction upon receipt of an electrical signal arriving at contraction generator  14 . Controller  16  has at least one input from contraction sensor  12  and is configured to output the electrical signal to contraction generator  14  upon receipt of output from contraction sensor indicative of a circumferential contraction. 
         [0025]    Contraction sensor  12  comprises a first set of electrodes  22  implanted in stomach  18 . First set of electrodes  22  are implanted circumferentially around a first circumference  24  defined by a radius  26  about gastric axis  28  in stomach  18 . First set of electrodes  22  may comprise any number of electrodes, although a number greater than one is preferred. Electrodes of first set of electrodes  22  may be positioned transverse one another in order to afford maximum sensitivity to a circumferential contraction. If two electrodes are employed, this means that the electrodes are spaced diametrically around first circumference  24 . Contraction generator  14  comprises a second set of electrodes  30  implanted in stomach  18 . Second set of electrodes  30  are implanted circumferentially around a second circumference  32  defined by a radius  34  about gastric axis  28 . Second set of electrodes  30  may comprise any number of electrodes, although a number greater than one is preferred. Electrodes of second set of electrodes  30  may be positioned transverse one another in order to afford maximum efficiency in invoking a circumferential contraction. If two electrodes are employed, this means that the electrodes are spaced diametrically around second circumference  32 . Sets of electrodes  22  and  30  are provided as sets of stainless steel electrodes (commonly available such as Temporary Cardiac Pacing Wire, Weck Cardiac Pacing Wires, Research Triangle Park, N.C., USA). Sets of electrodes  22  and  30  may be subserosally implanted at both sides of the anterior wall of antrum  38  of stomach  18  during laparotomy. Alternatively, gastric stimulator  10  may be implanted without surgical techniques. Each set of electrodes  22  and  30  comprises 1-cm active and reference electrodes. A second set of electrodes  30  may for example be positioned two—three cm proximal to pylorus  40 , with first set of electrodes  22  positioned three—four cm proximal second set of electrodes  30 . Controller  16  is configured to apply to second set of electrodes  30  an electrical current that overrides natural contractions of stomach  18 . Controller  16  may also be configured to apply the electrical current to first set of electrodes  22  as well. 
         [0026]    Controller  16  may be a custom-designed external neurostimulator. Controller  16  may include custom-designed hardware and software modules developed to implement a two-channel feedback-controlled neural gastric electrical stimulator. The controlling software may be designed using software such as Labview (National Instruments, Austin, Tex., USA). Both sets of electrodes  22  and  30  may be employed in applying electrical currents to stomach  18 . Referring to  FIG. 2 , controller  16  generates two-channel, controlled, charge-balanced bipolar rectangular voltage waveforms at a frequency of 50 Hz with an adjustable amplitude, duty cycle, on- and off-time and overlap between channels. By sequentially activating the channels (each channel corresponding to one of sets of electrodes  22  and  30 ), the direction of propagation of an invoked circumferential contraction can be controlled. Preferentially, second set of electrodes  30  are activated first, in order to initiate retrograde circumferential contractions that prevent food from being peristaltically emptied from stomach  18 . Controller  16  is implemented in software and the synthesized digital waveforms may be converted to voltages by a digital to analog converter such as a DAQCard-AI-16XE-50 (National Instruments, Austin, Tex., USA). A simple analog buffer amplifier provides the necessary current. 
         [0027]    Referring to  FIG. 1 , controller  16  may be configured to sense a natural circumferential contraction of stomach  18  in a number of ways. Controller  16  may be configured to measure impedance between electrodes of first set of electrodes  22 . In this case, first set of electrodes  22  may not only measure the impedance between electrodes but may also apply stimulation in concert with second set of electrodes  30 . Alternatively, gastric stimulator  10  may include a set of force transducers  46  and  48 . Force transducers  46  and  48  may be implanted on the anterior gastric wall along gastric axis  28 , three and a half to four cm apart. Force transducers  46  and  48  are located at different points on the inside of stomach  18 . As shown in  FIG. 1 , force transducer  46  is located at a point on first circumference  24 , while force transducer  48  is located on a third circumference  50  defined by a radius  52  about gastric axis  28  in stomach  18 . Alternatively, force transducers  46  and  48  may be located along any other circumference of stomach  18 , provided that force transducer  46  is located proximal second circumference  32 , and force transducer  48  is located proximal force transducer  46 . Force transducers  46  and  48  measure the force of deformation of the stomach wall in order to detect a circumferential contraction. Force transducers  46  and  48  may be strain gauge transducers, examples of which can be purchased from RB Products (Stillwater, Minn., USA). Recordings from transducers  46  and  48  may be acquired using a custom-designed analog bridge amplifier with frequency bandwidth between 0 and 1 Hz and digitized using a 10-Hz sampling frequency, and may be acquired by custom-designed software. The strength of gastric contractions, which is a measure of the spontaneous propulsive gastric motility, is assessed directly with the proximal force transducer, and indirectly with the interelectrode impedance of the proximal implanted channel. 
         [0028]    NGES for the treatment of obesity is based on the idea of overriding spontaneously existing slow waves by invoking local retrograde contractions to delay gastric emptying. However, spontaneously-existing propulsive gastric motility is a rather infrequent process, only active in the period after a meal and in some of the four phases of the migrating motor complex. Therefore, a feedback mechanism for NGES control is very beneficial for retrieving the timing of the spontaneously-existing contractile activity and adjusting the NGES timing accordingly. 
         [0029]    Bioimpedance has been routinely quantified as: 
         [0000]      =z L/A   [1] 
         [0000]    where Z is the electrical impedance of the tissue [Ω] having both a resistive and a reactive (capacitive) component, Z is its specific impedance [Ω cm], L is the distance between the centers of the measuring electrodes [cm], and A is the tissue cross sectional area [cm 2 ]. 
         [0030]    When electrical tissue properties are relatively constant over time, it is possible to estimate volumes encompassed by transversely positioned electrodes. Because antral contractions decrease the cross-sectional area at the location of a contraction and due to the specific electrode implantation technique that used, interelectrode impedance can be a measure of contraction strength in the vicinity of a given transversely-implanted electrode pair. In general, the tissue impedance between a transversely-implanted electrode pair is frequency dependent, and this is manifested by the presence of a capacitive component. Referring to  FIG. 4 , a model that is commonly used in the literature comprises a resistor  76  in parallel with a non-ideal capacitor  78 . The resistive component represents the conductive characteristics of the extracellular body fluid, while the reactive component has its complex origin in the cellular membranes which act as leaky, non-ideal capacitors. When measuring the impedance, an interrogating low-frequency current cannot pass through the cellular membranes and can only flow through the extracellular fluid. Alternatively, an interrogating high-frequency current can pass the cellular membranes resulting in a combined intra- and extracellular conductive pathways. The impedance of smooth muscle tissue is in the range of 10 2  to 10 3  Ω cm for frequencies between 100 Hz and 10 MHz. Referring to  FIG. 1 , with the transversally-implanted electrodes first set of electrodes  22  located for example four to five cm apart, the inter-electrode impedance as a measure for the contractile strength at their vicinity can then be used in the feedback loop. The frequency may be selected so that the difference between no contraction and maximum contraction is the highest. This frequency may be determined experimentally in the case of the electrode configuration shown. By using an impedance measurement system that is frequency-adjustable, with a minimum of about 5 kHz, influence of other bioelectric signals like ECG, EEG and EMG may be avoided and likewise stimulation of muscles and nerves may be avoided. Frequency maximum in this case is about 500 kHz, limited by the parasitic capacitances between the electrode leads as well as these between the ground and the measured object. 
         [0031]    The impedance measurement device may include a voltage controlled oscillator (VCO) to control the oscillation frequency. The output voltage of this VCO may be applied to the gastric tissue via first set of electrodes  22  when NGES is not taking place. The current through the tissue may be measured and converted into voltage by a transimpedance amplifier. 
         [0032]    a. Voltage Controlled Oscillator (VCO) 
         [0033]    In the present design an integrated circuit such as MAX038 (Maxim Integrated Products Inc., Sunnyvale, Calif., USA) may be used for the VCO. If the integrated circuit is a current-controlled oscillator whose frequency depends on the provided current and on an external capacitor, oscillation bandwidth may be controlled by selection of the capacitor, for example by using a quad digital switch such as a MAX4679 (Maxim Integrated Products Inc., Sunnyvale, Calif., USA). The output voltage delivered by the oscillator may be 2 Vpp constant over the entire frequency range. 
         [0034]    Along with the sinusoidal output, the VCO may be selected to provide a synchronous and a  90 -degrees out of phase quadrature square wave output. If these outputs are not of the same magnitude and have a DC offset, a highpass filter and a comparator (such as a MAX903 (Maxim Integrated Products Inc., Sunnyvale, Calif., USA) may be used to convert the synchronous and quadrature waves to equal amplitude outputs. The signals may be high-pass filtered if the comparator has an output offset. 
       Transimpedance Amplifier 
       [0035]    In the embodiment shown, the current through the tissue flows to the virtual ground of a transimpedance amplifier and is converted to a voltage by a resistor connecting the inverting input to the output of the amplifier. 
         [0036]    a. Synchronous Demodulation 
         [0037]    Current flow through the time-dependent inter-electrode impedance can be regarded as an amplitude modulated (AM) signal. By demodulating the signal, the amplitude and the phase of the inter-electrode impedance may be retrieved. Assuming that the voltage across the tissue is: 
         [0000]      ( t )= V  cos 2 πf   c   t    [2] 
         [0000]    where V is the stimulation voltage amplitude [V], f c  is the frequency of the stimulating signal [Hz] and t is time [s], the current through the tissue is then given by: 
         [0000]      ( t )= I ( t )cos 2 πf   c   t +σ( t )= I ( t )cos σ( t )cos 2 πf   c   t−I ( t )sin σ( t )sin 2 πf   c   t    [3] 
         [0038]    Referring to  FIG. 5 , synchronous demodulation may be performed by multiplying the retrieved signal by the synchronous and the 90-degrees de-phased signal and then low pass filtering the result. The low pass filters may be simple first-order RC filters, and may be employed to filter out any parasitic signal component with doubled frequency introduced by the multiplying operation. 
         [0039]    After introducing: 
         [0000]        R ( t )=( V /( I ( t )cos σ( t ))) −1  and  X ( t )=( V/ ( I ( t )sin σ( t ))) −1 ,  [4] 
         [0000]    so that V*R(t) and V*X(t) are the in-phase and the quadrature components of i(t), the measured impedance is Z(t)=V/i(t), where R(t) and X(t) are the resistive and the reactive components of Z(t), respectively. 
         [0040]    Referring to  FIG. 11 , a method of inducing controlled gastro paresis is illustrated. In step  54 , a circumferential contraction of stomach  18  is sensed at a first location on stomach  18 . The first location corresponds to first circumference  24  where first set of electrodes  22  are located. Step  54  may involve sensing a circumferential contraction by measuring the impedance between first set of electrodes  22  implanted in stomach  18 . Alternatively, step  54  may involve sensing a circumferential contraction by measuring the force of deformation of the wall of stomach  18 . In step  56 , a circumferential contraction is invoked in response to the sensed circumferential contraction of step  54 . The invoked circumferential contraction is invoked at a second location on stomach  18  closer to pylorus  40  than the first location. Second location corresponds to second circumference  32  where second set of electrodes  30  are located. The contraction is invoked in the antrum of the stomach. In step  56 , invoking a contraction comprises applying an electrical current to stomach  18  at second circumference  32 . In addition, an electrical current may be applied to stomach  28  at a third location, the third location being further from pylorus  40  than the second location. The third location may correspond to first circumference  24 , and the electrical current may be applied by first set of electrodes  22 . Alternatively, the third location may correspond to a different location, and may be applied using an additional electrode set-up. The invoked contraction overrides the naturally occurring circumferential contraction sensed at first circumference  24 . 
         [0041]    Referring to  FIG. 13 , a method for sensing a circumferential contraction using the impedance of the wall of stomach  18  is illustrated. In step  58 , the impedance is measured along a circumference of the wall of stomach  18 . This may be accomplished as described above using first set of electrodes  22 . In step  60 , the measured impedance is compared to a threshold value. Since impedance will decrease during a circumferential contraction, if the measured impedance is above the threshold value, than the method returns to step  58  and re-measures the impedance. This process is repeated, until a measured impedance value is returned that is below the threshold value. Referring to  FIG. 10A , because impedance measurements tend to drift over time, it may be necessary to process the measured impedance prior to comparing it to the threshold value. This processing may involve subtracting a moving average from the measured impedance, in order to compensate for drift variations in the measured impedance. The moving average may be calculated using the past twenty seconds of measured impedance values. Alternatively, other ranges of time of measured impedance values may be used to calculate the moving average. Additionally, a different processing method other than subtracting a moving average may be employed, such as higher-end statistical calculations. Referring to  FIG. 13 , once a circumferential contraction has been sensed, as indicated by a processed measured impedance value below the threshold value, a signal is sent to invoke a contraction in step  62 . 
         [0042]    An embodiment of the impedance measurement device was tested on a piece of beef tripe (not shown) to find the optimal interrogation frequency. Two electrodes were placed on the tripe  5  cm apart and a frequency sweep from 5 kHz to 500 kHz was performed. After the first sweep the tripe was pulled together so that the inter-electrode distance was reduced to 2.5 cm. Another frequency sweep was performed to find the impedance in this contracted state. Referring to  FIG. 8 , the results from both sweeps are depicted. The change from extracellular to intracellular conduction was estimated at the relatively low frequency of 6 kHz. There was no change in the phase of the impedance. The inter-electrode impedance difference between contracted and uncontracted states was approximately 350 Ω for all frequencies, indicating there was no favorable frequency. The small deflection at 35 kHz was caused by switching of the VCO capacitors at that frequency. Finally, a frequency of 50 kHz was chosen, which is considered a preferred frequency for single frequency bioimpedance measurements. 
         [0043]    Referring to  FIG. 8 , the baseline impedance value drifted over time. To compensate for this phenomenon a 20-second moving average was calculated and subtracted from the actual impedance. Referring to  FIGS. 9A-9C , the adjusted impedance values for first set of electrodes  22  showed good correlation with the force measurements of force transducers  46  and  48  (r=0.6, p&lt;0.001). The deviations resulting from natural and NGES-induced contractions are in the 100-Ω order of magnitude. Referring to  FIGS. 10A-10C  the results gastric stimulator  10  using an inter-electrode impedance-based feedback system are shown. Measurements for force transducers  46  and  48  are included only to provide proper illustration, and need not be employed with gastric stimulator  10 . A trigger level  86  for the impedance measurements was reversed, since the inter-electrode impedance decreases during natural contraction  80 . Similarly to the results with force-based feedback, invoked contractions  84  triggered by the impedance feedback were higher in amplitude then natural contractions  80 . Invoked gastro paresis was also observed after the inter-electrode impedance-based feedback was activated. 
         [0044]    The method illustrated in  FIG. 13  may also be used to sense a circumferential contraction anywhere in the gastrointestinal tract, substituting pylorus  40  with the rectum (not shown) of the patient, and stomach with the gastrointestinal tract. In this case, a contraction may be invoked along a second circumference (not shown) of the gastrointestinal tract, as defined by a radius (not shown) of gastric axis  28 , the second circumference being closer to a rectum (not shown) than the first circumference (not shown). A contraction may be invoked, as before, by applying an electrical current to the gastrointestinal tract along the second circumference. Additionally, an electrical current may also be applied to the gastrointestinal tract along either the first circumference, or along a third circumference (not shown) defined by a radius (not shown) of the gastrointestinal tract. If the electrical current is also applied along the first circumference, it may be done so using the same electrodes that originally sensed the circumferential contraction. 
         [0045]    Referring to  FIG. 14 , a method for sensing a circumferential contraction using the force of deformation of the wall of stomach  18  is illustrated. In step  64 , the force of deformation of the wall of stomach  18  is measured. This measuring is done using force transducer  46 , or both of force transducers  46  and  48 . In step  66 , the measured force is compared to a threshold value. Since the force will increase during a circumferential contraction, if the measured force is below the threshold value, than the method returns to step  64  and re-measures the force of deformation. This process is repeated, until a measured force value is returned that is above the threshold value. Referring to  FIG. 10B , because force measurements can drift over time, it may be necessary to process the measured force prior to comparing it to the threshold value. This processing may involve subtracting a moving average from the measured force, in order to compensate for drift variations in the measured force. The moving average may be calculated using the past twenty seconds of measured force values. Alternatively, other ranges of time of measured force values may be used to calculate the moving average. Additionally, a different processing method other than subtracting a moving average may be employed, such as higher-end statistical calculations. Referring to  FIG. 14 , once a circumferential contraction has been sensed, as indicated by a processed measured force value above the threshold value, a signal is sent to invoke a contraction in step  68 . 
         [0046]    The feedback loop using force transducers  46  and  48  was able to control the NGES timing. Referring to  FIGS. 6A and 6B , when a natural circumferential contraction  80  at force transducer  48  reached a stimulation threshold  82 , controller  16  was turned on and initiated an NGES at time  83 , producing a retrograde circumferential contraction  84  starting at second set of electrodes  30 . Before contraction  80  could reach force transducer  46 , NGES-invoked retrograde contraction  84  was produced which overrode the propulsive contraction. The magnitudes of electrically-invoked contractions  84  exceeded the magnitudes of natural circumferential contractions  82 , as measured by force transducers  46  and  48 . If a natural contraction occurred within 40 seconds from the last stimulation, invoked retrograde contraction  84  was lower in amplitude, indicating that a refractory period of 20 seconds was probably not sufficient for repeated stimulation. Referring to  FIGS. 7A and 7B  the frequency of natural contractions  80  significantly diminished immediately after the first NGES-invoked retrograde contraction  84  was administered, a phenomenon that could be regarded as NGES-invoked gastro paresis. 
         [0047]    Referring to  FIG. 12 , another method of inducing controlled gastro paresis is illustrated. In step  70 , a circumferential contraction is sensed at a first location on the stomach, in a similar fashion as that described for step  54  in  FIG. 11 . In step  72 , a circumferential contraction is invoked at a second location in response to the sensed circumferential contraction, in a similar fashion as that described for step  56  in  FIG. 11 . In step  74 , a refractory period is observed after step  72 . The refractory period may be longer than twenty seconds, in order to prevent stomach  18  from adapting to the gastric stimulation applied it. Steps  70 ,  72  and  74  may now be repeated until it is desirable to cease. It may be advantageous to employ the method described in  FIG. 12  in addition to the method described above for sensing a circumferential contraction anywhere in the gastrointestinal tract. That way, a retrograde circumferential contraction can be induced to override a natural circumferential contraction at any desirable point in the gastrointestinal tract. 
         [0048]    These above measurements (impedance in  FIG. 13 , force of deformation in  FIG. 14 ) were used to control the NGES using a level-based threshold which signalled controller  16  to produce a retrograde stimulating pattern starting from the distally implanted second set of electrodes  30 . The threshold level of the trigger was set at a fixed value and was turned on when the difference between the instantaneous feedback signal and its moving average over the last 20 seconds reached this value. This subtraction of the moving average from the instantaneous feedback signal representing gastric motility was introduced to remove the drift of the feedback variable. After each triggered stimulation sequence a refractory period of 20 seconds was imposed to give the gastric tissue the chance to recover from the NGES. Referring to  FIGS. 3A and 3B , block-diagrams of the overall feedback-controlled NGES technique used in the study are illustrated. Referring to  FIG. 3A , gastric stimulator  10  employs the use of force transducers  46  and  48  to sense circumferential contractions. Referring to  FIG. 3B , gastric stimulator  10  senses circumferential contractions using the impedance measured between electrodes of first set of electrodes  22 . 
         [0049]    In this document, two different feedback mechanisms, a force-based feedback control and an inter-electrode impedance-based feedback control are utilized to improve the effectiveness of retrograde NGES for the treatment of obesity. Both methods were tested in acute canine experiments and were able to control the timing of controller  16  in a very similar and comparable fashion. 
         [0050]    In an implantable gastric stimulator  10 , an inter-electrode impedance-based feedback system may be preferred over a force based feedback setup in order to keep the surgical procedures minimally invasive and to reduce the technological requirements to the device. Further, the inter-electrode impedance-based feedback employs the same sets of electrodes  22  and  30  used for stimulation and therefore no extra wires have to be implanted. Only minimal hardware enhancement of an implantable NGES device would be required to practically implement such system. 
         [0051]    The invoked gastro paresis observed in this document shows the potential of this apparatus and method to reduce food intake by delaying gastric emptying. The reduced frequency of spontaneously-existing gastric contractions  80  disturbed on demand by the NGES-invoked retrograde contractions  84  are the main factor contributing to delaying gastric emptying which in turn could provoke early satiety and reduced food intake. 
         [0052]    A previous chronic animal study of NGES for the treatment of obesity (Aelen P., et al., “Manipulation of Food Intake and Weight Dynamics Using Retrograde Neural Gastric Electrical Stimulation in a Chronic Canine Model, Neurogastroenterology and Motility”) showed adaptation of the gastric smooth muscle when stimulated with the same voltage amplitude level over several days. With the feedback loop closed, stimulation would only be applied in the presence of a natural contraction of pre-determined strength, instead of continuously stimulating (and fatiguing) the smooth muscle. These fewer NGES-invoked contractions would probably make it less likely to cause muscle adaptation to the applied voltage stimulation levels. Further, if muscle adaptation still occurs over a longer period of time, the voltage amplitude of stimulation can be adjusted to a higher level by measuring the amplitude of the invoked contractions with the feedback mechanism itself. In addition to the reduced chance of muscle adaptation by this more efficient way of stimulation, the demands on the batteries of the implant would be significantly lower. Another energy saving possibility could be found in the amplitude of stimulation. The amplitudes of the invoked retrograde contractions were higher then these of the Erythromycin-driven contractions, and the voltage amplitude of stimulation could probably be lowered to produce a contraction of similar strength to a natural contraction. This in turn would have a positive effect on the energy demands for implantable gastric stimulator  10 , would further reduce the muscle adaptation problem, and would diminish further the refractory time so that the state of invoked gastroparesis could be achieved faster and more efficiently. 
         [0053]    Two separate feedback methods explored the controllability of gastric stimulator  10 . A force transducer-based feedback method and inter-electrode impedance based feedback method both were both able to measure circumferential gastric contractions and to control the timing of stimulation in order to invoke retrograde contractility leading to temporary gastro paresis during eating. The inter-electrode impedance-based feedback method uses the implanted stimulating electrodes for stimulation, making it a preferred technique to embed in an implantable autonomous neurostimulator. 
         [0054]    In the claims, the word “comprising” is used in its inclusive sense and does not exclude other elements being present. The indefinite article “a” before a claim feature does not exclude more than one of the feature being present. Each one of the individual features described here may be used in one or more embodiments and is not, by virtue only of being described here, to be construed as essential to all embodiments as defined by the claims. Immaterial modifications may be made to the embodiments described here without departing from what is covered by the claims.