1. Proprioception-Related Evoked Potentials Presented by Efrat Barak

2. Objectives The objectives of this work are: To introduce Proprioceptive Evoked Potentials (PEPs) and their stimulation, recording, and analysis techniques. To introduce Proprioceptive Evoked Potentials (PEPs) and their stimulation, recording, and analysis techniques. To discuss the differences between PEPs and sensory evoked potentials (SEPs) that are elicited by electrical nerve stimulation. To discuss the differences between PEPs and sensory evoked potentials (SEPs) that are elicited by electrical nerve stimulation.

3. What Are Proprioceptive Evoked Potentials? Proprioception is “ sensing the body ”, Proprioception is “ sensing the body ”, i.e. gathering information about: The body ’ s position in space The body ’ s position in space Active and passive movements Active and passive movements Force that is applied by the body Force that is applied by the body Such data is collected by receptors of the somatosensory system, named proprioceptors, which report on stretching of muscles and angles of joints. For example, muscle spindles and Golgi tendon organs are proprioceptors. Such data is collected by receptors of the somatosensory system, named proprioceptors, which report on stretching of muscles and angles of joints. For example, muscle spindles and Golgi tendon organs are proprioceptors. Due to independent studies of EPs related to proprioception, a number of different terms have emerged in this field: [Arnfred et al., 2000; Bear et al., 2001]

4. Termination The most common terms are: Proprioceptive Evoked Potentials (PEPs) are potentials evoked by addition of weight to a hand held load. [Arnfred, et al., 2000] Proprioceptive Evoked Potentials (PEPs) are potentials evoked by addition of weight to a hand held load. [Arnfred, et al., 2000] Proprioceptive Event Related Potentials (PERPs) are potentials evoked by a stimulation similar to the former one, but with an oddball paradigm [Arnfred, 2005] Proprioceptive Event Related Potentials (PERPs) are potentials evoked by a stimulation similar to the former one, but with an oddball paradigm [Arnfred, 2005] Proprioception-related evoked potentials are potentials evoked by passive body movements [Seiss et al., 2002] Proprioception-related evoked potentials are potentials evoked by passive body movements [Seiss et al., 2002] For convenience, the term Proprioceptive Evoked Potentials (PEPs) will be used here to describe all potentials evoked by stimulation of proprioceptors, e.g. EPs evoked by active or passive movements. Notice that this does not include potentials evoked by electrical stimulation.

5. Example: PEPs Related to Finger Movement Bötzel et al. [1997] studied potentials evoked by finger movement in 11 healthy subjects. Post-movement potentials were evoked by three stimulation methods: The subject actively moved his right middle finger to a given position (active movement). The subject actively moved his right middle finger to a given position (active movement). The finger was passively stretched by a technician that pulled a string that was tapped to the finger (passive movement). The finger was extended to the same position as in (1), in a comparable velocity. The finger was passively stretched by a technician that pulled a string that was tapped to the finger (passive movement). The finger was extended to the same position as in (1), in a comparable velocity. The median nerve was electrically stimulated, The median nerve was electrically stimulated, and the somatosensory evoked potentials (SEPs) were recorded.

6. Example: PEPs Related to Finger Movement During stimulation, EEG was recorded from the scalp using the 10-20 system. During stimulation, EEG was recorded from the scalp using the 10-20 system. Source analysis was performed using Source analysis was performed using the BESA program. Results: The active and passive EPs were very similar, and both included an N2/P2 complex at about 80ms after stimulus onset (Fig. 1), with stronger P2 in the passive case. The active and passive EPs were very similar, and both included an N2/P2 complex at about 80ms after stimulus onset (Fig. 1), with stronger P2 in the passive case. In the SEPs, N20/P20 complex was identified (data not shown). In the SEPs, N20/P20 complex was identified (data not shown). Fig. 1. Thick line – recording from electrode 3. Thin line – finger acceleration trace.

7. Example: PEPs Related to Finger Movement Fig. 2. Average dipole locations. Back - active movement N2/P2 dipole. Light grey - passive movement N2/P2 dipole. Dark grey - median nerve SEP N20/P20 dipole. The angular part signals the range of orientations of the positive dipoles ends. The dipoles of the N2/P2 and the N20/P20 complexes were attributed to the same area in the contralateral hemisphere, but differed in dipole orientation (Fig. 2): The dipoles of the N2/P2 and the N20/P20 complexes were attributed to the same area in the contralateral hemisphere, but differed in dipole orientation (Fig. 2): SEPs N20/P20 dipole pointed anterior-medially. SEPs N20/P20 dipole pointed anterior-medially. Active and passive N2/P2 dipoles pointed posteriorly. Active and passive N2/P2 dipoles pointed posteriorly.

8. Example: PEPs Related to Finger Movement Discussion: Because the EPs of the active and passive stimuli were very similar, they must be purely somatosensory (a motor component would have appeared in the active condition only). What is the origin of this somatosensory information? Cutaneous afferents and joint afferents are ruled out because they usually do not report joint position. Cutaneous afferents and joint afferents are ruled out because they usually do not report joint position. Golgi tendon organs are also not an option, because they are not modulated by passive joint movements. Golgi tendon organs are also not an option, because they are not modulated by passive joint movements. Primary muscle spindle afferents of the forearm are the best candidates. Primary muscle spindle afferents of the forearm are the best candidates. By contrast, it has been established that the median nerve SEPs originates in cutaneous and joint receptors, and has very little contribution from muscle spindles [Seiss et al. 2003].

9. Example: PEPs Related to Finger Movement Conclusion: The N2/P2 complex arises from cerebral processing of proprioceptive information sent from muscle spindles to the brain. Therefore, the potentials elicited by passive and active movements are PEPs. Conclusion: The N2/P2 complex arises from cerebral processing of proprioceptive information sent from muscle spindles to the brain. Therefore, the potentials elicited by passive and active movements are PEPs. Interestingly, the dipole analysis indicated that the proprioceptive information arrives to S1. This result will later be compared to those of other researches. Interestingly, the dipole analysis indicated that the proprioceptive information arrives to S1. This result will later be compared to those of other researches.

10. Example II: PEPs Related to Wrist Movement Arnfred et al. [1999] studied potentials evoked by a change of load that the subject held (Fig 3). Fig. 3. Experimental set-up Stimulation: linear increment of the load from 400g to 480g, in steps of 20g in 10ms. The maximal load (480g) was maintained for 100ms. The stimulus was described as ‘ carrying a basket of apples when another apply is suddenly thrown into it ’. Stimulation: linear increment of the load from 400g to 480g, in steps of 20g in 10ms. The maximal load (480g) was maintained for 100ms. The stimulus was described as ‘ carrying a basket of apples when another apply is suddenly thrown into it ’. EEG was recorded from 10 right-handed subjects using the 10-20 system EEG was recorded from 10 right-handed subjects using the 10-20 system

11. Example II: PEPs Related to Wrist Movement Results: the major components of the EPs were (Fig. 4): Contralateral parietal waves P70\P190 at C3 ’ Contralateral parietal waves P70\P190 at C3 ’ Frontal N70 wave at Fz Frontal N70 wave at Fz P100 wave at Cz P100 wave at Cz Discussion: The pattern of very close frontal and parietal activation with reverse polarities resembles the PEPs of passive movements that were recorded by Bötzel et al. [their data is not shown], and is significantly different from median nerve SEPs. The pattern of very close frontal and parietal activation with reverse polarities resembles the PEPs of passive movements that were recorded by Bötzel et al. [their data is not shown], and is significantly different from median nerve SEPs. Fig. 4. Grand average of the EPs. Arrows mark stimulus onset.

12. Example II: PEPs Related to Wrist Movement Moreover, the stimulus was perceived as applied force, i.e. neither tactile nor passive movement. Moreover, the stimulus was perceived as applied force, i.e. neither tactile nor passive movement. Conclusion: A brisk change of hand held load elicits PEPs with intermediate latency. In a later work, Arnfred [2005] studied the EPs elicited by a similar method, using an oddball paradigm. The subjects had to recognize the type of stimulus (frequent: +40g / rare: +100g) and count the oddball stimuli. This study showed that P100 of the two stimuli hardly differed, while later components were influenced by the context. Since P100 is related to specific processing in S2 cortex, the author concluded that the proprioceptive stimulus is processed within the first 100ms.

13. Sensitivity of PEPs to Movement Parameters Seiss et al. [2002] studied the influence of movement parameters on PEPs elicited by passive movements. Stimulation was performed by a robot that imposed four types of passive finger movements (Fig 5): Extension to 15mm Extension to 15mm Extension to 25mm Extension to 25mm Flexion to 15mm Flexion to 15mm Flexion to 25mm Flexion to 25mm During stimulation, EEG was recorded using the 10-20 system. Additionally, the authors recorded median nerve SEPs elicited by electrical stimulation. Fig. 5. The robot that imposed passive finger movements. [Seiss et al., 2003]

14. Sensitivity of PEPs to Movement Parameters Results: All PEPs elicited by the four passive movement stimuli were similar, with a frontal negative wave measured at electrode FC1 at about 90ms (denoted N90). All PEPs elicited by the four passive movement stimuli were similar, with a frontal negative wave measured at electrode FC1 at about 90ms (denoted N90). The four PEPs differed only in the wave duration: N90 was about 30ms longer for 25mm stimuli than for 15mm stimuli. Movement direction did not matter (Fig. 6). The four PEPs differed only in the wave duration: N90 was about 30ms longer for 25mm stimuli than for 15mm stimuli. Movement direction did not matter (Fig. 6). This prolongation was roughly This prolongation was roughly proportional to the difference between the movement durations. The SEP showed the well known The SEP showed the well known N20/P20 pattern. Fig. 6. PEP grand average. Solid line – 15mm stimulus, dashed line – 25mm stimulus.

15. Sensitivity of PEPs to Movement Parameters Source analysis yielded a single dipole for each PEP. The dipoles were in close proximity, and were anterior to the source of the SEP. Source analysis yielded a single dipole for each PEP. The dipoles were in close proximity, and were anterior to the source of the SEP. Moreover, the analysis showed that the PEPs are generated in the motor cortex. Moreover, the analysis showed that the PEPs are generated in the motor cortex.Conclusion: The authors suggested the following: longer movements may give rise to contributions of other neuronal populations to the PEP, which are not revealed in PEPs elicited by short movements.

16. Conclusion: PEPs Features Several corollaries can be made from the described studies: PEPs reflect the arrival and processing of proprioceptive information at the cortex. PEPs reflect the arrival and processing of proprioceptive information at the cortex. PEPs can be elicited by: PEPs can be elicited by: Active movements Active movements Passive movements Passive movements Weight lifting Weight lifting Muscle stretching (which was not discussed here) Muscle stretching (which was not discussed here) However, electrical stimulation elicits SEPs, not PEPs. It has been recently suggested that the first 100ms of PEPs reflects processing of the proprioceptive stimulus, and later components are changed by the context. It has been recently suggested that the first 100ms of PEPs reflects processing of the proprioceptive stimulus, and later components are changed by the context.

17. Conclusion: PEPs Features The pattern of PEPs: The pattern of PEPs: Comparing the described studies indicates that PEPs are usually characterized by a frontal negative component. The latency of this component varies between different experiments, probably due to differences in the stimulation techniques and the body part that is moving. Comparing the described studies indicates that PEPs are usually characterized by a frontal negative component. The latency of this component varies between different experiments, probably due to differences in the stimulation techniques and the body part that is moving. Passive and active movements yield PEPs that are very similar, both in latencies and in amplitudes. Passive and active movements yield PEPs that are very similar, both in latencies and in amplitudes. While a number of studies concluded that PEPs are generated in the sensory cortex, a recent study indicated that PEPs also have contributions from the motor cortex. While a number of studies concluded that PEPs are generated in the sensory cortex, a recent study indicated that PEPs also have contributions from the motor cortex.

18. Comparison of PEPs and Electrically Evoked SEPs Origin: PEPs reflect input from muscle spindle afferents only. On the contrary, median nerve SEPs reflect inputs from cutaneous afferents, as well as negligible inputs from muscle spindle afferents. Practically, it can be assumed that PEPs and SEPS reflect different inputs [Seiss et al., 2003]. Origin: PEPs reflect input from muscle spindle afferents only. On the contrary, median nerve SEPs reflect inputs from cutaneous afferents, as well as negligible inputs from muscle spindle afferents. Practically, it can be assumed that PEPs and SEPS reflect different inputs [Seiss et al., 2003]. Pattern: The primary component of PEPs has a frontal-negative distribution, while the N20/P20 component of the median nerve SEP has a parietal-negative/frontal-positive distribution. Pattern: The primary component of PEPs has a frontal-negative distribution, while the N20/P20 component of the median nerve SEP has a parietal-negative/frontal-positive distribution. Cortical generator: N2/P2 components of PEPs are generated in the sensorimotor cortrex, and their source is 7-10 mm anterior to the source of N20/P20 complex of the median nerve SEPs. Cortical generator: N2/P2 components of PEPs are generated in the sensorimotor cortrex, and their source is 7-10 mm anterior to the source of N20/P20 complex of the median nerve SEPs.

19. The Benefit in PEPs Research Investigation of PEPs seems to hold promise in two fields: 1. Movement disorders. analysis of PEPs isolates information about the proprioceptive feedback that exists in the sensory-motor loop. Thus, PEPs investigation may improve our understanding of movement disorders such as Huntington ’ s disease and Parkinson ’ s disease. 2. Neuropsychiatric disorders. Since the perception of ‘ myself ’ is established on integration of proprioceptive and sensory information, PEPs can be utilized for investigating neuropsychiatric disorders, e.g. schizophrenia. [Arnfred, 2005; Seiss et al., 2003]

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