Hindlimb Motor Responses Evoked by Dual-Electrode

Intraspinal Microstimulation in the Cat

Warren M. Grill¹ and Michel A. Lemay²

¹Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA

²Department of Neurobiology and Anatomy, MCP Hahnemann University, Philadelphia, PA, USA

wmg@po.cwru.edu, Michel.Lemay@drexel.edu

Abstract

Intraspinal microstimulation of the grey matter evokes organized patterns of isometric force at the endpoint of a multi-joint limb. The purpose of the present study was to quantify the rules of combination for endpoint force patterns produced by co-stimulation of two intraspinal electrodes. We measured the endpoint force patterns in decerebrate cats evoked by individual stimulation and co-stimulation, and quantified the results using 3 models of force response combination: linear summation, winner-take-all, and weighted linear summation. Winner-take-all was the dominant rule for combination of force responses evoked by co-stimulation.

1. Introduction

Intraspinal microstimulation of interneuronal regions in the frog [1], rat [5], and cat [2] generates organized patterns of endpoint isometric force. These responses involve contraction of multiple muscles, and comparable responses have not been observed following stimulation of individual muscles. The purpose of the present experiments was to determine whether isometric force responses produced by 2 individual intraspinal electrodes could be combined to produce new force responses by co-stimulation of both electrodes.

Previous measurements in chronic spinal frogs [3, 4] and rats [5] found that the response produced by co-activation of two spinal sites was either the vectorial summation of the forces produced by the activation of each site individually (linear summation) or identical to the response obtained by stimulating one of the individual sites (winner-take-all), with the linear combination response being most prevalent [3, 4]. We compared the response during co-activation of two sites with the responses produced by activation of each individual site in decerebrate cats, and found that winner-take-all responses were prevalent in this preparation.

2. Methods

Acute experiments were conducted in decerebrate cats to measure the motor responses evoked by stimulation using two independent intraspinal microelectrodes. The animals were initially anaesthetized with ketamine (25 mg/kg), and anesthesia maintained using halothane. A laminectomy was performed to expose the lumbar spinal cord, and the contralateral limb was denervated. The animal was mounted in a stereotaxic frame, a mid-collicular decerebration was performed, and Halothane then discontinued. Cord and core temperatures were maintained at 38°C, the cord was bathed in mineral oil, and blood pressure and expired CO₂ were monitored throughout the experiment.

The animal’s spine and pelvis were immobilized, and the paw attached to a gimball mounted on a six-degree of freedom force/moment transducer. The transducer was mounted at the endpoint of a two degree-of-freedom robot that held the paw isometric during force measurements.

Motor responses were elicited by intraspinal microstimulation with trains of biphasic current pulses (train duration: 0.5 s, frequency: 40Hz, pulse duration: 100µsec, pulse amplitude: 10-100µA). At selected depths along each electrode penetration the limb was moved from a mid-stance position to nine to twelve endpoint locations on a 3cm grid. At each location force responses were recorded while stimulation parameters and electrode position were kept constant. The forces measured at nine to twelve endpoint locations were used to calculate by interpolation [1] the forces at the limb end-point throughout that workspace.

Co-stimulation experiments were conducted using 2 independent microelectrodes with one always positioned ipsilateral to the limb on which forces are measured, and the other positioned either on the ipsilateral or contralateral side. Both electrodes were at depths of 600-1200 µm, and positioned 1-2 cm from each other. The individual responses for each electrode were measured at one activation level and nine limb positions. The responses produced by co-activation of both sites with the stimulation levels used for the individual responses were also measured.

The relationship between the force responses evoked by stimulation of the individual sites and the responses evoked by co-stimulation of two sites was tested against three hypotheses:

1) summation hypothesis: the response during co-stimulation was the scaled vector sum of the observed individual force responses, i.e. Fab = s[Fa +Fb], where Fa and Fb represent the fields obtained by individual stimulation at sites a and b, respectively, and Fab represents the field obtained via co-stimulation of site a and site b. s was obtained by least-squares estimation.

2) winner-take-all hypothesis: the response during co-stimulation was a scaled version of one of the individual responses, i.e. Fab = min|| Fab - s (Fa OR Fb)||.

3) weighted summation hypothesis: the response during co-stimulation was a weighted vector sum of the observed individual force responses, i.e. Fab = s₁Fa + s₂Fb, where s₁ and s₂ are the scaling factor for each of the individual fields, obtained by east-squares estimation.

3. Results

An example of the responses evoked by stimulation of two intraspinal sites is presented in fig. 1. The ipsilateral electrode produced a caudal flexion response (Fa), while the contralateral electrode produced a caudal extension response (Fb). The forces obtained during co-stimulation of both sites, as well as the optimal fit for each of the three models: linear summation, winner-take-all, and weighted sum, are also illustrated. The parameters for the best fit of each of the models were s=-0.045 for the linear sum, s=1.56 for the winner-take-all with the ipsilateral site winning, and s₁=1.60 (ipsilateral site) and s₂=.03 (contralateral site) for the weighted summation. The negative scaling coefficient for the linear summation is indicative of how poor the fit was for that model, and the average residual for the forces (x & y force coefficients) was 0.586 N. Both the winner-take-all and weighted sum models reproduced well the actual co-stimulation response, and the average force residual was ~0.1 N for both models. In the weighted sum model, the scaling coefficient for the contralateral response (Fb) was very low, indicating that the contralateral site’s response does not contribute to the response during co-activation of the two sites. Thus, this is an example of a winner-take-all combination of force responses.

This example was representative of results from 7 response sets collected across five experiments. From 5 ipsilateral-contralateral force response sets, co-stimulation resulted in winner-take-all responses in 4 cases, and a non-linear response in 1 case. In the non-linear case, the combination of forces was position dependent. From 2 ipsilateral-ipsilateral force response sets, co-stimulation resulted in winner-take-all responses in both cases

Figure 1: Force patterns evoked by individual stimulation of two spinal sites (Fa, Fb), co-stimulation of the two sites (Fco), and the best-fit force patterns of each of the three field combination models. Each panel shows the pattern of endpoint force vectors over the workspace of the limb. The x and y position of a vector corresponds to the x and y position of the endpoint of the limb, the length of each arrow corresponds to the force magnitude, and the direction of each arrow corresponds to the direction of the endpoint force.

3. Summary and Conclusions

Microstimulation of interneuronal regions in the grey matter of the spinal cord evokes organized patterns of isometric force at the limb endpoint. The purposes of the present study were to determine whether new endpoint force patterns could be produced by co-stimulation of two intraspinal electrodes, and to quantify the rules of combination of the individual force patterns during co-stimulation. We measured the endpoint force patterns in decerebrate cats evoked by individual stimulation and co-stimulation, and quantified the results using 3 models of force response combination: linear summation, winner-take-all, and weighted linear summation.

In contrast to previous findings in frog [3, 4] and rat [5] indicating that linear combination was the dominant rule of combination, in the decerebrate cat, winner-take-all was the dominant rule for combination of the force responses evoked by co-stimulation. These results suggest that the repertoire of motor responses that can be generated by microstimulation may be limited by the non-linear interaction between responses produced by individual electrodes.

Acknowledgment

This work was supported by the NIH Neural Prosthesis Program (NS-8-2300).

References

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[2] Lemay, MA, WM Grill (1999) Spinal force fields in the cat spinal cord. Society for Neuroscience Abstracts 25:1396.

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[4] Mussa-Ivaldi, F. A., S. F. Giszter, E. Bizzi (1994) Linear combinations of primitives in vertebrate motor control, Proc. Natl. Acad. Sci. USA, 91:7534-7538.

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