Patent Document:

fig1 illustrates an implantable device 100 suitable for implementing the present invention . device 100 comprises an implanted control unit 110 , which controls application of neural stimuli , and controls a measurement process for obtaining a measurement of a neural response evoked by the stimuli from each of a plurality of electrodes . device 100 further comprises an electrode array 120 consisting of a three by eight array of electrodes 122 , each of which may be selectively used as either the stimulus electrode or sense electrode , or both . fig2 is a schematic of a feedback controller which refines future stimuli based on estimated recruitment of neurons by past stimuli . the present embodiment provides for the recruitment estimator in fig2 to obtain a measurement of a masked neural response arising in response to a probe stimuli applied during a refractory period of a therapeutic stimulus , and also provides for measurement of an unmasked neural response arising in response to a probe stimuli applied after a refractory period of the same or equivalent subsequent therapeutic stimulus . comparing the ratio or difference between the masked and unmasked neural responses indicates a level of recruitment achieved by the therapeutic stimulus . in this embodiment the evoked cap measurements are made by use of the neural response measurement techniques set out in the australian provisional patent application no . 2011901817 in the name of national ict australia ltd entitled “ method and apparatus for measurement of neural response ” from which the present application claims priority . long pulse widths on the order of 400 μs , as used in many commercially available stimulators , cause problems for the measurement of evoked response , as much of the neural response passes the recording electrodes during the stimulus period . that is , in such a biphasic pulse , at least 0 . 8 ms passes from stimulus onset before measurement is possible . as shown in fig3 a , the therapeutic stimulus 302 continues for a sufficiently long period of time that it substantially temporally overlaps the evoked neural response 304 . the signal amplitudes in fig3 are not to scale , and the therapeutic stimulus is of the order of volts while the neural response measurement is of the order of tens of microvolts , so that in the case shown in fig3 a the evoked response is practically impossible to measure directly . nevertheless , for many reasons it is desirable to measure or estimate the amplitude of the response r t induced by stimulus 302 . fig3 b and 3 c illustrate the masked to unmasked stimulation paradigm provided by the present embodiment of the invention . in order to estimate how many fibres are recruited in the neural response 304 arising from the long therapeutic pulse 302 , a shorter probe pulse 306 is delivered shortly after the therapeutic stimulus 302 . the neural response 308 caused by probe pulse 306 is not contemporaneous with any stimulus , and is therefore able to be measured without being swamped by large stimulus voltages . notably , by delivering the probe pulse 306 during the refractory period of the fibres triggered in response 304 , the response 308 has an amplitude r i which is proportional to the number of fibres which were not triggered by the long pulse 302 . after a time delay of sufficient length to allow all fibres triggered as part of either response 304 or response 308 to exit their refractory states , another short probe pulse 310 is delivered as shown in fig3 c . probe pulse 310 preferably has the same parameters as probe pulse 306 . obtaining a measure of response 312 provides an unmasked response amplitude measurement r s , with r s & gt ; r i , against which the first , masked response 308 can be compared . this masked / unmasked ratio ( r i : r s ) can be used to estimate what proportion of the accessible fibre population was stimulated in response 304 by therapeutic stimulus 302 , thereby allowing r t to be estimated . notably , when performed sufficiently quickly that a fibre - to - electrode distance will remain substantially constant , this technique is not susceptible to the problem of unknown fibre - to - electrode distance as the ratios cancel the effect of variable electrode - to - fibre distance . in addition to determining recruitment of long pulse width stimuli , it can be useful to measure physiological parameters such as refractory periods in order to give a diagnosis of various conditions or diseases . thus , in another embodiment of the invention the refractory period is estimated by first obtaining a measure r s of the unmasked neural response to a given probe stimulus . then , two stimuli are applied close together separated by a variable delay t d ( fig3 b ). with increasing t d , the amplitude r i can be expected to markedly increase when the onset of pulse 306 is delayed sufficiently to allow the average refractory period of the neural population recruited in response 304 to conclude , so that observing such an increase in r i allows that population &# 39 ; s refractory period to be estimated . there are a number of neurological conditions and non - neurological conditions which can affect the refractory period . this measurement technique may thus serve as a useful diagnostic indicator . fig4 illustrates recordings of actual evoked responses in accordance with the embodiment of fig3 . the recordings of a response pair were made on 8 spaced apart electrodes along the spinal column as the evoked responses 404 , 408 travelled along the spinal column adjacent to the array . as can be seen , an initial response 404 is evoked by a first stimulus , and then a second response 408 is evoked immediately afterwards in the refractory period of the neural population recruited as part of response 404 . response 408 is of reduced , but non - zero , amplitude . the relative ratios of the amplitudes of the measurements of the two responses thus permit the above - described information to be elicited . fig5 is a plot of the ( p1 - n1 ) amplitude of measurements of responses 502 , 506 respectively evoked by a first pulse 302 and a second pulse 306 of equal amplitude and pulse width , for varying inter - stimulus interval t d . as can be seen at 502 , the first pulse 302 produces the same recruitment and response amplitudes irrespective of t d . however , the recruitment effected by the second pulse 306 varies considerably with t d , as shown by 506 . two fibre population characteristics are evident in this plot , either or both of which may be investigated in accordance with the present invention in order to determine suitable stimulus parameters and / or physiological state or change . first , pulse 302 will depolarise some fibres close to threshold , but without activating them . this partial depolarisation means that for small t d , in the range ( 512 ) of about 0 to 200 μs , where pulse 306 is sufficiently close in time to pulse 302 , some fibres that had not been activated by 302 may be activated by 306 more easily than is the case for the remainder of the refractory period for t d & gt ; 200 μs . this depolarisation will decay with time , usually to resting levels before the end of the absolute refractory period for the fibres that were activated by 302 . this means for short inter - stimulus intervals ( e . g . & lt ; 200 us ), there will be a response 308 from fibres which had residual depolarisation from 302 . second , for t d greater than about 400 μs , a relative refractory period 514 commences , during which fibres activated by 302 gradually become able to be activated again . between the remnant depolarisation period 512 and the relative refractory period 514 , the absolute refractory period dominates and the second pulse 306 is almost entirely unable to recruit any response ( it is noted that curve 506 is at levels around 5 μv in this period which may be noise and does not necessarily indicate any response has been evoked ). thus assessing curve 506 instantaneously permits a current state of both ( a ) the residual depolarisation decay 512 , and ( b ) onset of the relative refractory period 514 to be assessed . monitoring curve 506 over time permits changes in these characteristics to be determined , for example to be used for feedback to optimise therapeutic stimuli or in order to diagnose or monitor an underlying disease . while fig3 b shows the probe pulse 306 as having the same amplitude as therapeutic pulse 302 , alternative embodiments may advantageously use probe pulses 306 and / or 310 which are of a different amplitude to therapeutic pulse 302 . for example , therapeutic pulse 302 is usually set to a comfortable level for the patient , and at such a level not all fibres are usually recruited by pulse 302 . pulse 306 may therefore be set to have a greater amplitude and / or a greater total charge than therapeutic stimulus 302 in order to ensure that the probe pulse 306 will recruit at least some fibres even when applied during the refractory period of fibres recruited as part of response 304 . in another embodiment the probe stimulus 306 may be configured to have reduced recruitment capability as compared to pulse 302 , so that if pulse 306 is applied during the absolute refractory period of fibres recruited as part of response 304 then pulse 306 will recruit no additional response . in such embodiments , when the relative delay t d is such that probe stimulus 306 occurs in the relative refractory period of response 304 , being the period in which some fibres recruited as part of response 304 have concluded their refractory period but some have not , then the probe stimulus response 308 will begin to recruit fibres . determining the value of t d at which a threshold exists for response 308 starting to arise provides useful information regarding the refractory period of response 304 . routinely , during assessment of patients for spinal cord stimulation therapy , the patient will undergo a trial stimulation procedure . this is where the patient is implanted with a percutaneous lead with an externalised set of contacts . the lead is attached to an external pulse generator and the patient has use of the device for several days . at the end of the trial period the clinician and patient assess the performance of the system with regard to pain relief and a choice is made whether or not to proceed with a full implantation . the take - home device for trial purposes may consist of both a stimulus generator but also an evoked response measurement system . the ert responses recorded during the trial period could be used to adjust the stimulus parameters as described above . the ert system measures amplitude growth functions etc ., collected at time of surgery and during the trial stimulation period , and together with subjective performance measures could be used to develop a correlation between the response parameters and the patient outcomes . for instance , there is considerable variation in threshold response and there may exist a correlation between threshold and outcome where lower thresholds generate better outcomes . there are a large number of neurological parameters that can be collected in performing ert measures , including refractory periods . systematic collection of this data across a number of patients will allow analysis for correlation with outcome . it will be appreciated by persons skilled in the art that numerous variations and / or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described . for example the neural response measurement may be conducted in accordance with any suitable cap measurement technique . the present embodiments are , therefore , to be considered in all respects as illustrative and not restrictive .

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