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PW3-1 CHEPs: psychophysics, brain dynamics and clinical applications
S86 electromyography studies provide valuable information regarding the functional status of nerves, they do not provide information on nerve morphology. Ultrasonography provides an inexpensive, non-invasive means of obtaining high quality images in the electromyography laboratory. The fusion of the two technologies will ultimately lead to a better understanding of peripheral nerve disease. Due to improvements in imaging technology over the last decade, it is now possible to visualize commonly tested nerves of the upper and lower extremities. In this talk, the background for the development and use of peripheral nerve ultrasound will be discussed. Images of normal upper and lower extremity peripheral nerves will be presented, including median, ulnar, radial, and peroneal nerves. Images of the normal brachial plexus will also be presented. The characteristics of nerves affected by compression, trauma and dysimmune disease will be discussed, along with images of entrapment neuropathies, variant anatomy, neuromas, and polyneuropathies. Relevant research supporting the use of peripheral nerve ultrasonography will be reviewed. PW2-2 Ultrasonography in the diagnosis of upper extremity nerve entrapment syndromes J.S. Yoon1 1 The physical medicine and rehabilitation department, Korea university hospital at Guro, Korea Recently high resolution ultrasound becomes more feasible and accurate for the evaluation of entrapment of upper extremity nerves. It allows the anatomic assessment of nerve pathology with advantage of noninvasive, painless, radiation-free and portable manner. This is the reason why ultrasound has been used commonly for the evaluation of carpal tunnel syndrome (CTS) and ulnar neuropathy at the elbow (UNE) in upper extremity. In this workshop, I will present a brief description of the normal ultrasound (US) anatomy of the upper peripheral nerves, and discuss about the US appearance of the most frequent disorders of nerve entrapment in upper extremities. In general, basic US findings of peripheral nerve will be shown. Dynamic nature of nerves and related structures in normal will be discussed. Each nerve will be visualized and measured along its entire course. At the wrist level, the proximal and distal area of the carpal tunnel delimited by carpal bone will be shown. Nerves and tendons will also be visualized. Then following each nerves to forearm and elbow level, nerves and related structures will be shown. In focal entrapment neuropathy such as CTS or UNE, the US findings are usually presented as swelling or loss of axonal fibril pattern. For evaluating the swelling of nerves, the cross sectional area (CSA) of each nerves (median, ulnar and radial) at each level will be measured. The ratio between proximal and distal CSA of median nerve will be estimated. Especially in UNE, the displacement of ulnar nerve should be checked because it may cause false negative result in nerve conduction study. This bias can be minimized via using US. With showing of median and ulnar nerves, radial nerve will be shown by some cases of traumatic injury. PW2-3 Moving toward morphofunctional measures of the peripheral nerve L. Padua1 Department of Neurosciences, Universita’ Cattolica del Sacro Cuore, Rome, Italy
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Looking at the future of the wedding between ultrasound (US) and neurophysiology we have to keep in mind two main topics. Despite numerous studies on the role of ultrasound in nerve assessment, we know very little about the US changes when related to temporal evolution but even to neurophysiological alterations as axonal loss and myelin alterations. Neurophysiology and US have helped to address diagnostic questions, but we still lack reliable information on prognosis. How does US pattern change during the course of the disease? Has axonal damage a different US appearance from demyelisation? Until now neurophysiological and US findings followed parallel paths, but is it possible to combine such differing parameters? The creation of novel indexes through the mathematical merger of the functional (velocity, amplitude) and the morphological (diameters, cross sectional area, perimeter) measures might provide new tools to evaluate the peripheral nerve, providing information on both: diagnosis and prognosis. Recently, diagnostic imaging approach has dramatically improved its potential following the rate of computer technology evolution. If neurophysiologists are dealing with imaging as a mean to give a morphologic correlation
Oral Presentations: Proposed Workshops to their functional parameters, imaging is also evolving toward new functional objectives. We are really convinced that integration of parameters derived from the sum of the two techniques will open soon outstanding and unexpected points of view: if we are dealing with the nerve in a new perspective (From square to cube, Padua and Martinoli, 2009), in the next future we will probably have to sculpt the cube into a sphere in which neurophysiologic and US dimensions are no longer distinct, but fused as one. After all, who is more accustomed to dealing with a compound response than neurophysiologists? PW2-4 Ultrasound of the brachial plexus N. van Alfen1 1 Dept. of Neurology and Clinical Neurophysiology, RU Nijmegen Medical Center, The Netherlands Ultrasound of the brachial plexus is a recent contribution to the field of peripheral nervous system ultrasound. It was mainly developed by anesthesiologists in need of direct visualization of the plexus to perform better and safer locoregional nerve blocks. Its use in diagnosing or monitoring neuromuscular disorders is still in its infancy, but shows promise in specific disorders, such as demyelinating or inflammatory neuropathies such as CIDP. The most common transducer used is a linear probe in the 10 18 MHz frequency range, providing sufficient resolution up to 5 cm depths. US cannot image the brachial plexus as a whole, but is usually performed in 4 discrete regions: the interscalene region showing the nerve roots and trunks, the supraclavicular region for a view of the anterior and posterior divisions, the infraclavicular approach to the cords, and the axillary region to visualize the terminal branches. The nerve elements are best viewed in a short-axis or crosssectional plane, where the epineurium and connective tissues appear hyperechoic (white) and the nerve fascicles as relatively hypoechoic (black) dots, giving the whole a stippled or honeycomb-like appearance. Pathologic nerves generally become enlarged and diffusely hypoechoic. With sufficient training discontinuous nerve elements such as in trauma or focal thickening seen in entrapment or tumors can be visualized. PW2-5 Advances in skeletal muscle ultrasound S. Pillen1 , N. Van Alfen1 Radboud University Nijmegen Medical Centre, Donders Centre of Neuroscience, Department of Neurology, Nijmegen, The Netherlands
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Muscle ultrasound is a convenient technique to visualize normal and pathological muscle tissue as it is non-invasive and real-time. Neuromuscular disorders give rise to structural muscle changes that can be visualized with ultrasound: atrophy can be objectified by measuring muscle thickness, while infiltration of fat and fibrous tissue increase muscle echo intensity, i.e. the muscles become whiter on the ultrasound image. Muscle echo intensity need to be quantified to correct for agerelated increase in echo intensity and differences between individual muscles. This can be done by gray scale analysis, a method that can be easily applied in daily clinical practice. Using this technique it is possible to detect neuromuscular disorders with predictive values of 90 percent. Only in young children and metabolic myopathies the sensitivity is lower. Ultrasound is a dynamic technique and therefore capable of visualizing normal and pathological muscle movements. Fasciculations can easily be differentiated from other muscle movements. Ultrasound appeared to be even more sensitive in detecting fasciculations compared to EMG and clinical observations, because it can visualize a large muscle area and deeper located muscles. With improving resolution and frame rate it has recently become clear that also smaller scale spontaneous muscle activity such as fibrillations can be detected by ultrasound. This opens the way to a broader use of muscle ultrasound in the diagnosis of peripheral nerve and muscle disorders. PW3. Contact heat-evoked potentials (CHEP) PW3-1 CHEPs: psychophysics, brain dynamics and clinical applications A.C.N. Chen1 1 Center for Higher Brain Functions, Department of Neurobiology, Capical Medical University, Beijing, China Contact heat evoked potentials (CHEPs), first published in 1991, has been in science exactly for a decade. It now evolves into three main themes:
29th International Congress of Clinical Neurophysiology psychophysics, brain dynamics, and pathophysiological applications. In psychophysics, the simulation sites, intensities, spatial field, temporal summation on pain ratings and CHEPS indicate systematic effects, along with gender and age. The conduction velocity is estimated as in the A-delta and c-fiber category. In brain dynamics, the N1-P1-N2 complex is consistently seen and the N1-P1 amplitude correlates with pain perception. However, the reported peak latencies vary across labs to be a function of the stimulus factors and subject conditions. The peak stages of brain responses show the focal maxima of the N1 and P1 at vertex Cz and N2 at parietal Pz in topographical mappings. Source imaging demonstrates two peak activations for the vertex N550/Cz and P750/Pz components: the supplementary motor area, SMA BA-6 source for N550, and posterior cingulate BA-23 for P750 in source imaging, respectfully. In an fMRI report, CHEPS are consistent with thermal pain studies of BOLD changes in the insula, post-central gyrus, supplementary motor area (SMA), middle cingulate cortex and pre-central gyrus. The values of psychophysics and results from brain dynamics strongly support the feasibility and validity for use of CHEPS in clinical examinations of patients, as reports of CHEPS in trigeminal neuropathic pain, carpal tunnel syndrome, sensory neuropathy, skin-denerved neuropathic pain, fibromyalgesia, meralgia paresthetica, Kennedy disease, but not abnormal in the ALS. Coming next, it requires proof of the prognosis utility and therapeutic correlates in CHEPS for robust clinical applications.
S87 Brain 129:977, 2006; Chao et al, J Neurol Neurosurg Psychiatry 79:97, 2008). There had been limited approaches to assess the physiology and pathology of painful neuropathies. We have applied CHEP and skin biopsy to investigate physiological mechanisms and pathological correlations of painful neuropathy. In patients with painful neuropathies (diabetic and idiopathic in etiologies), the CHEP amplitude was linearly correlated with IENF density and thermal thresholds, with the most significant correlation between the CHEP amplitude and IENF density (p < 0.001). CHEP amplitude corresponded significantly to intensity of pain perception. In relation to the characteristics of neuropathic pain, CHEP amplitude was higher in patients with thermal hyperalgesia compared to patients without (p = 0.01) although similar IENF density between them. In conclusion, skin biopsy with quantiation of IENF density provides pathologic evidence of painful neuropathy due to cutaneous nerve degeneration. Both approaches are complementary in assessing the physiology and pathology of painful neuropathy due to cutaneous nerve degeneration. PW3-4 Heat evoked potentials for the diagnosis of neuropathic pain and hypersensitivity disorders P. Anand1 Imperial College London, London, UK
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PW3-2 Upper and lower limb Ad fiber conduction velocities by contact heat evoked potential stimulation (CHEPS) B.E. Smith1 , M.A. Ross1 , C. Hoffman-Snyder1 Department of Neurology, Mayo Clinic, Scottsdale, Arizona, USA
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Objective: To document limb Ad fiber conduction velocities in neurologically normal individuals. Methods: Individuals with normal neurologic examinations (neuropathy impairment scores of 0; 0 = normal) and no neurologic symptoms underwent contact heat evoked potential stimulation (CHEPS) testing. Twelve limbs (6 arms and 6 legs) were studied from three subjects (2F, 1M, mean age 43 years). Latencies and CV values of N1 from limb stimulation sites to the contralateral scalp (Cz-tied ears) were determined. At each site 14 stimuli were administered to obtain an averaged scalp response. Results: Reproducible responses were obtained from all sites in all limbs tested. The median CV in m/s (range; standard deviation) from the various sites were: foot 3.46 (2.71 3.75; 0.47), leg 2.89 (1.95 3.14; 0.48), thigh 2.59 (1.74 2.80; 0.43), hand 2.23 (1.58 2.52; 0.42), forearm 1.75 (0.99 1.87; 0.39), and arm 1.22 (0.55 1.32; 0.32). CV values were greatest from the distal site, intermediate from the middle site, and least from the proximal site in all twelve limbs. Conclusions: Even though painful peripheral neuropathy involving small diameter fibers is common, there are few noninvasive techniques to quantify abnormalities in somatic small fiber neural pathways. Contact heat evoked potential stimulation (CHEPS) provides a straightforward, safe, noninvasive method to assess somatic Ad fiber pathways. Median normal limb Ad fiber CV values are reported, showing a decreasing distal to proximal gradient in CV. CHEPS records small diameter Ad fiber pathway responses (amplitude, latency and CV) in individuals with conditions involving small diameter fibers. Studies are underway to augment the cohort of normal controls. PW3-3 Overview of pain-related evoked potentials on neuropathic pain S.-T. Hsieh1 1 Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan Injury to small-diameter nociceptive nerves is a major mechanism causing neuropathic pain, particularly diabetic neuropathy, AIDS neuropathy, and neuropathies due to chemotherapeutic agents, such as taxol and cisplatin. Contact heat evoked potential (CHEP) provides a physiological approach to assess painful neuropathy (Chao et al, Clin Neurophysiol 119:653, 2008). The incorporation of CHEP and fMRI demonstrates distinct and shared brain activation patterns on innocuous and noxious heat stimulations (Tseng et al, Hum Brain Mapp in press, 2010). Because these fibers terminate in the skin, several groups including ours have established skin biopsy with quantitation of intraepidermal nerve fiber density (IENF density) as a pathologic diagnosis of smallfiber sensory neuropathy (Shun et al, Brain 127:1593, 2004; Tseng et al,
Heat evoked potentials have advanced the diagnosis of painful small fiber sensory neuropathies, and helped to distinguish these from other chronic pain and hypersensitivity disorders, such as fibromyalgia. Contact heat evoked potentials have recently been shown to provide critical diagnostic information in painful radiculopathies i.e. “small fiber variants e Syndrome”, when other objective measures such as of the Guillain Barr´ skin biopsies and flare responses may be normal. Thus contact evoked potentials are an essential tool for the comprehensive assessment of patients with neuropathic pain and hypersensitivity. When combined with functional MRI and the array of other measures including quantitative sensory testing, heat evoked potentials can also play an important role in the development of new treatments, serving as a biomarker for pain and small sensory fiber regeneration. Our recent studies have shown a correlation of heat evoked potential amplitudes with skin nerve fibres expressing GAP-43, which is a selective marker of regenerating nerve fibres (in a human volunteer model of topical skin application of capsaicin with serial heat evoked potentials and skin biopsy studies). Classical skin nerve fiber structural markers such as PGP9.5 did not show such a correlation. We have also developed a new human volunteer model acute topical skin application of capsaicin of “neuropathic pain” leads to decreased amplitutude of heat evoked potentials, but increased areas of activation of cerebral regions involved with pain processing by fMRI, a pattern observed in some patients with neuropathic pain and hypersensitivity. Heat evoked potentials may thus serve as a useful objective non-invasive diagnostic test, and a biomarker for the development of new treatments for pain and nerve regeneration. PW4. The role of the medial frontal cortex in valuation and social interaction PW4-1 Medial frontal cortex and decision-making: evidence from primate neuropsychology and neurophysiology S.W. Kennerley1,2,3 , P.H. Rudebeck3,4 , M.E. Walton3 , M.F.S. Rushworth3 , J.D. Wallis2 1 Institute of Neurology, Sobell Dept., University College London, London, UK, 2 Helen Wills Neuroscience Institute & Dept. of Psychology, UC Berkeley, Berkeley, CA, USA, 3 Dept. of Experimental Psychology, Oxford University, Oxford, UK, 4 Lab. of Neuropsychology, Natl. Inst. of Mental Health-National Inst. of Hlth., Bethesda, MD, USA Objective: Whether making economic choices between different goods, or making choices in how we interact in social situations, optimal behavior relies on a valuation system which can formulate accurate predictions about the expected value of potential behavioral outcomes. Although damage to areas of the prefrontal cortex particularly anterior cingulate cortex (ACC) and orbital frontal cortex (OFC) impairs decisionmaking in a variety of contexts, brain damage in humans is rarely restricted to a single area, clouding the issue as to how different frontal lobe regions contribute to decision-making in different contexts.
1
Looking at the future of the wedding between ultrasound (US) and neurophysiology we have to keep in mind two main topics. Despite numerous studies on the role of ultrasound in nerve assessment, we know very little about the US changes when related to temporal evolution but even to neurophysiological alterations as axonal loss and myelin alterations. Neurophysiology and US have helped to address diagnostic questions, but we still lack reliable information on prognosis. How does US pattern change during the course of the disease? Has axonal damage a different US appearance from demyelisation? Until now neurophysiological and US findings followed parallel paths, but is it possible to combine such differing parameters? The creation of novel indexes through the mathematical merger of the functional (velocity, amplitude) and the morphological (diameters, cross sectional area, perimeter) measures might provide new tools to evaluate the peripheral nerve, providing information on both: diagnosis and prognosis. Recently, diagnostic imaging approach has dramatically improved its potential following the rate of computer technology evolution. If neurophysiologists are dealing with imaging as a mean to give a morphologic correlation
Oral Presentations: Proposed Workshops to their functional parameters, imaging is also evolving toward new functional objectives. We are really convinced that integration of parameters derived from the sum of the two techniques will open soon outstanding and unexpected points of view: if we are dealing with the nerve in a new perspective (From square to cube, Padua and Martinoli, 2009), in the next future we will probably have to sculpt the cube into a sphere in which neurophysiologic and US dimensions are no longer distinct, but fused as one. After all, who is more accustomed to dealing with a compound response than neurophysiologists? PW2-4 Ultrasound of the brachial plexus N. van Alfen1 1 Dept. of Neurology and Clinical Neurophysiology, RU Nijmegen Medical Center, The Netherlands Ultrasound of the brachial plexus is a recent contribution to the field of peripheral nervous system ultrasound. It was mainly developed by anesthesiologists in need of direct visualization of the plexus to perform better and safer locoregional nerve blocks. Its use in diagnosing or monitoring neuromuscular disorders is still in its infancy, but shows promise in specific disorders, such as demyelinating or inflammatory neuropathies such as CIDP. The most common transducer used is a linear probe in the 10 18 MHz frequency range, providing sufficient resolution up to 5 cm depths. US cannot image the brachial plexus as a whole, but is usually performed in 4 discrete regions: the interscalene region showing the nerve roots and trunks, the supraclavicular region for a view of the anterior and posterior divisions, the infraclavicular approach to the cords, and the axillary region to visualize the terminal branches. The nerve elements are best viewed in a short-axis or crosssectional plane, where the epineurium and connective tissues appear hyperechoic (white) and the nerve fascicles as relatively hypoechoic (black) dots, giving the whole a stippled or honeycomb-like appearance. Pathologic nerves generally become enlarged and diffusely hypoechoic. With sufficient training discontinuous nerve elements such as in trauma or focal thickening seen in entrapment or tumors can be visualized. PW2-5 Advances in skeletal muscle ultrasound S. Pillen1 , N. Van Alfen1 Radboud University Nijmegen Medical Centre, Donders Centre of Neuroscience, Department of Neurology, Nijmegen, The Netherlands
1
Muscle ultrasound is a convenient technique to visualize normal and pathological muscle tissue as it is non-invasive and real-time. Neuromuscular disorders give rise to structural muscle changes that can be visualized with ultrasound: atrophy can be objectified by measuring muscle thickness, while infiltration of fat and fibrous tissue increase muscle echo intensity, i.e. the muscles become whiter on the ultrasound image. Muscle echo intensity need to be quantified to correct for agerelated increase in echo intensity and differences between individual muscles. This can be done by gray scale analysis, a method that can be easily applied in daily clinical practice. Using this technique it is possible to detect neuromuscular disorders with predictive values of 90 percent. Only in young children and metabolic myopathies the sensitivity is lower. Ultrasound is a dynamic technique and therefore capable of visualizing normal and pathological muscle movements. Fasciculations can easily be differentiated from other muscle movements. Ultrasound appeared to be even more sensitive in detecting fasciculations compared to EMG and clinical observations, because it can visualize a large muscle area and deeper located muscles. With improving resolution and frame rate it has recently become clear that also smaller scale spontaneous muscle activity such as fibrillations can be detected by ultrasound. This opens the way to a broader use of muscle ultrasound in the diagnosis of peripheral nerve and muscle disorders. PW3. Contact heat-evoked potentials (CHEP) PW3-1 CHEPs: psychophysics, brain dynamics and clinical applications A.C.N. Chen1 1 Center for Higher Brain Functions, Department of Neurobiology, Capical Medical University, Beijing, China Contact heat evoked potentials (CHEPs), first published in 1991, has been in science exactly for a decade. It now evolves into three main themes:
29th International Congress of Clinical Neurophysiology psychophysics, brain dynamics, and pathophysiological applications. In psychophysics, the simulation sites, intensities, spatial field, temporal summation on pain ratings and CHEPS indicate systematic effects, along with gender and age. The conduction velocity is estimated as in the A-delta and c-fiber category. In brain dynamics, the N1-P1-N2 complex is consistently seen and the N1-P1 amplitude correlates with pain perception. However, the reported peak latencies vary across labs to be a function of the stimulus factors and subject conditions. The peak stages of brain responses show the focal maxima of the N1 and P1 at vertex Cz and N2 at parietal Pz in topographical mappings. Source imaging demonstrates two peak activations for the vertex N550/Cz and P750/Pz components: the supplementary motor area, SMA BA-6 source for N550, and posterior cingulate BA-23 for P750 in source imaging, respectfully. In an fMRI report, CHEPS are consistent with thermal pain studies of BOLD changes in the insula, post-central gyrus, supplementary motor area (SMA), middle cingulate cortex and pre-central gyrus. The values of psychophysics and results from brain dynamics strongly support the feasibility and validity for use of CHEPS in clinical examinations of patients, as reports of CHEPS in trigeminal neuropathic pain, carpal tunnel syndrome, sensory neuropathy, skin-denerved neuropathic pain, fibromyalgesia, meralgia paresthetica, Kennedy disease, but not abnormal in the ALS. Coming next, it requires proof of the prognosis utility and therapeutic correlates in CHEPS for robust clinical applications.
S87 Brain 129:977, 2006; Chao et al, J Neurol Neurosurg Psychiatry 79:97, 2008). There had been limited approaches to assess the physiology and pathology of painful neuropathies. We have applied CHEP and skin biopsy to investigate physiological mechanisms and pathological correlations of painful neuropathy. In patients with painful neuropathies (diabetic and idiopathic in etiologies), the CHEP amplitude was linearly correlated with IENF density and thermal thresholds, with the most significant correlation between the CHEP amplitude and IENF density (p < 0.001). CHEP amplitude corresponded significantly to intensity of pain perception. In relation to the characteristics of neuropathic pain, CHEP amplitude was higher in patients with thermal hyperalgesia compared to patients without (p = 0.01) although similar IENF density between them. In conclusion, skin biopsy with quantiation of IENF density provides pathologic evidence of painful neuropathy due to cutaneous nerve degeneration. Both approaches are complementary in assessing the physiology and pathology of painful neuropathy due to cutaneous nerve degeneration. PW3-4 Heat evoked potentials for the diagnosis of neuropathic pain and hypersensitivity disorders P. Anand1 Imperial College London, London, UK
1
PW3-2 Upper and lower limb Ad fiber conduction velocities by contact heat evoked potential stimulation (CHEPS) B.E. Smith1 , M.A. Ross1 , C. Hoffman-Snyder1 Department of Neurology, Mayo Clinic, Scottsdale, Arizona, USA
1
Objective: To document limb Ad fiber conduction velocities in neurologically normal individuals. Methods: Individuals with normal neurologic examinations (neuropathy impairment scores of 0; 0 = normal) and no neurologic symptoms underwent contact heat evoked potential stimulation (CHEPS) testing. Twelve limbs (6 arms and 6 legs) were studied from three subjects (2F, 1M, mean age 43 years). Latencies and CV values of N1 from limb stimulation sites to the contralateral scalp (Cz-tied ears) were determined. At each site 14 stimuli were administered to obtain an averaged scalp response. Results: Reproducible responses were obtained from all sites in all limbs tested. The median CV in m/s (range; standard deviation) from the various sites were: foot 3.46 (2.71 3.75; 0.47), leg 2.89 (1.95 3.14; 0.48), thigh 2.59 (1.74 2.80; 0.43), hand 2.23 (1.58 2.52; 0.42), forearm 1.75 (0.99 1.87; 0.39), and arm 1.22 (0.55 1.32; 0.32). CV values were greatest from the distal site, intermediate from the middle site, and least from the proximal site in all twelve limbs. Conclusions: Even though painful peripheral neuropathy involving small diameter fibers is common, there are few noninvasive techniques to quantify abnormalities in somatic small fiber neural pathways. Contact heat evoked potential stimulation (CHEPS) provides a straightforward, safe, noninvasive method to assess somatic Ad fiber pathways. Median normal limb Ad fiber CV values are reported, showing a decreasing distal to proximal gradient in CV. CHEPS records small diameter Ad fiber pathway responses (amplitude, latency and CV) in individuals with conditions involving small diameter fibers. Studies are underway to augment the cohort of normal controls. PW3-3 Overview of pain-related evoked potentials on neuropathic pain S.-T. Hsieh1 1 Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan Injury to small-diameter nociceptive nerves is a major mechanism causing neuropathic pain, particularly diabetic neuropathy, AIDS neuropathy, and neuropathies due to chemotherapeutic agents, such as taxol and cisplatin. Contact heat evoked potential (CHEP) provides a physiological approach to assess painful neuropathy (Chao et al, Clin Neurophysiol 119:653, 2008). The incorporation of CHEP and fMRI demonstrates distinct and shared brain activation patterns on innocuous and noxious heat stimulations (Tseng et al, Hum Brain Mapp in press, 2010). Because these fibers terminate in the skin, several groups including ours have established skin biopsy with quantitation of intraepidermal nerve fiber density (IENF density) as a pathologic diagnosis of smallfiber sensory neuropathy (Shun et al, Brain 127:1593, 2004; Tseng et al,
Heat evoked potentials have advanced the diagnosis of painful small fiber sensory neuropathies, and helped to distinguish these from other chronic pain and hypersensitivity disorders, such as fibromyalgia. Contact heat evoked potentials have recently been shown to provide critical diagnostic information in painful radiculopathies i.e. “small fiber variants e Syndrome”, when other objective measures such as of the Guillain Barr´ skin biopsies and flare responses may be normal. Thus contact evoked potentials are an essential tool for the comprehensive assessment of patients with neuropathic pain and hypersensitivity. When combined with functional MRI and the array of other measures including quantitative sensory testing, heat evoked potentials can also play an important role in the development of new treatments, serving as a biomarker for pain and small sensory fiber regeneration. Our recent studies have shown a correlation of heat evoked potential amplitudes with skin nerve fibres expressing GAP-43, which is a selective marker of regenerating nerve fibres (in a human volunteer model of topical skin application of capsaicin with serial heat evoked potentials and skin biopsy studies). Classical skin nerve fiber structural markers such as PGP9.5 did not show such a correlation. We have also developed a new human volunteer model acute topical skin application of capsaicin of “neuropathic pain” leads to decreased amplitutude of heat evoked potentials, but increased areas of activation of cerebral regions involved with pain processing by fMRI, a pattern observed in some patients with neuropathic pain and hypersensitivity. Heat evoked potentials may thus serve as a useful objective non-invasive diagnostic test, and a biomarker for the development of new treatments for pain and nerve regeneration. PW4. The role of the medial frontal cortex in valuation and social interaction PW4-1 Medial frontal cortex and decision-making: evidence from primate neuropsychology and neurophysiology S.W. Kennerley1,2,3 , P.H. Rudebeck3,4 , M.E. Walton3 , M.F.S. Rushworth3 , J.D. Wallis2 1 Institute of Neurology, Sobell Dept., University College London, London, UK, 2 Helen Wills Neuroscience Institute & Dept. of Psychology, UC Berkeley, Berkeley, CA, USA, 3 Dept. of Experimental Psychology, Oxford University, Oxford, UK, 4 Lab. of Neuropsychology, Natl. Inst. of Mental Health-National Inst. of Hlth., Bethesda, MD, USA Objective: Whether making economic choices between different goods, or making choices in how we interact in social situations, optimal behavior relies on a valuation system which can formulate accurate predictions about the expected value of potential behavioral outcomes. Although damage to areas of the prefrontal cortex particularly anterior cingulate cortex (ACC) and orbital frontal cortex (OFC) impairs decisionmaking in a variety of contexts, brain damage in humans is rarely restricted to a single area, clouding the issue as to how different frontal lobe regions contribute to decision-making in different contexts.