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Estimation of neural architecture in human brain by means of the dipole tracing method
Neuroscience Letters, 136 (1992) 169-172 © 1992 Elsevier Scientific Publishers Ireland Ltd. All rights reserved 0304-3940/92/$ 05.00
169
NSL 08429
Estimation of neural architecture in human brain by means of the dipole tracing method Yoshio N a k a j i m a a, Saburo H o m m a a, Toshimitsu M u s h a b, Hiroshi Sasaki b and Yoshiwo O k a m o t o c ODepartment of Physiology, School of Medicine, Chiba University, Chiba (Japan), bDepartmentof Applied Electronics, Tokyo Institute of Technology, Yokohama (Japan) and CDepartmentof Electronics, Chiba Institute of Technology, Chiba (Japan) (Received 12 November 1991; Accepted 27 November 1991)
Key words: Dipole tracing; Depth electrode; Epileptic spike; Hippocampus; Neural structure The electric source locations of interictal spikes recorded with depth electrodes were estimated by the dipole tracing (DT) method. Threedimensional coordinates of the active surfaces of the depth electrodes and head geometry of the patient were measured from frontal and saggital X-ray images and by a special device, respectively. The estimated dipole locations were superimposed on MR images of the patients. The dipole locations estimated in the hippocampal or parahipocampal regions successively moved in a small limited region during the interictal spike's peak. It was suggested that an interictal spike is composed of summated equivalent dipoles generated by hypersynchronization of a cluster of neurons, and that the timing of such hyperexcitation is more or less delayed because of electrical propagation along neuronal clusters which might be separated by sclerotic tissues.
To estimate the location of an electric source generator (e.g. a current dipole) within the human brain, a new computer-aided method was developed [3, 5]. Activity of neural structures in a region of the brain was represented as one equivalent current dipole [1, 7]. This method, which is called dipole tracing (DT), enables one to estimate the locations and vector moments of such dipoles. To estimate the electric location of interictal spikes recorded from patients with electrodes inserted into the brain, a head model with an infinite and homogeneous conductivity was assumed in forward solution. Dipolarity of more than 98%, which indicates the accuracy of estimation as an equivalent current dipole [4], was adopted as being significant since such high dipolarity is assumed that the estimated dipole location and vector moment correspond with true ones [6]. The present study was performed after obtaining the informed consent from two patients with epilepsy at the National Epilepsy Center, Shizuoka Higashi Hospital, for neurological treatment. Four to 5 depth electrodes, each of which has 5 active surfaces at 5 mm intervals, were inserted into the brain approximately 1 week prior to EEG recordings. Interictal spikes were monopolarly and simultaneouly recorded with 19 out of 20 or 25 acCorrespondence: Y. Nakajima, Department of Physiology, School of Medicine, Chiba University, 1 8-1, Inohana, Chiba 280, Japan. Fax: (81) 472-22 7853.
tive surfaces. The interictal spikes thus recorded were analyzed using the DT method. 1. Three-dimensional coordinates of depth electrodes inserted in to the brain and the head geometry. Three-dimensional coordinates of the active surfaces of the depth electrodes were measured from frontal and saggital X-ray images taken during stereotactic surgical operation and by parallel X-ray irradiation. The reference point for coordinate measurement was set at the center of four stereotactic fixation points of the scalp which were set in parallel to the OM-line of the patient. The head geometry of a patient was measured by a specially designed device prior to surgical operation. The device was made of a semi-spherical helmet with 64 displacement sensors, by which three-dimensional coordinates of the tips of the sensors (that correspond with coordinates of outer surface of the head) were measured from a patient. The OM-line and mid-line of the helmet were adjusted to correspond with those of the patient prior to measurement. In Fig. 1A, the spatial relationships between the outermost out-line of the head measured by the device and the nineteen active surfaces of depth electrodes measured from X-ray images are shown on the horizontal sections of two patients, H and Y. The electrode positions, from which interictal spikes are actually recorded, are shown as open circles. 2. Dipole tracing of interictal spikes. As can be seen in
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Fig. 1. A: interictal spikes simultaneously recorded with depth electrodes indicated by open circles are shown in the horizontal section of the head in two patients H and Y. Estimated locations of the spike generator are also indicated by filled circles in the respective patient. B: estimated locations and vector moments on the three plains of the head of patient Y. PH, parahippocampus; H, hippocampus; A, amygdala; OF, orbitofrontal.
Fig. 1A (patient H), interictal spikes were recorded with high amplitude from the depth electrodes H and PH inserted into the left hippocampus and parahippocampus, respectively. Furthermore, the phase reversal was observed between electrode Nos. 2 and 3 of the depth electrode PH. (cf., The smaller the electrode number, the more medially the active surface is located.) These findings indicate that the generator of the spike lies between electrode Nos. 2 and 3 of the depth electrode PH. From the 19 recordings, the location of the spike generator was estimated by the DT method and the result is shown by filled circles in the horizontal section in Fig. 1A (left). The generator of the spike is estimated in the vicinity of electrode No. 3, between electrode Nos. 2 and 3. In the case of patient Y (right side of Fig. 1A), the high amplitude spike is selectively recorded from the depth electrode H inserted into the right hippocampus although the phase reversal was not clearly observed. The location of the spike generator estimated by the DT method is shown as filled circles in the horizontal section of patient H. In this case, the generator was estimated in the vicinity of electrode No. 2 of the depth electrode H. Fig. 1B shows the spatial relationship of the position
of the active surfaces, dipole locations and vector moments in horizontal, frontal and saggital sections of patient Y. The dipole locations and vector moments shown in Fig. 1B were calculated at 5 ms intervals around the interictal spike's peak. As can be seen in Fig. 1B, all of the estimated vectors were similarly directed. Four to 5 dipoles were estimated from a single spike of patient Y and they moved temporally and spatially within a narrow space. As can be seen in Fig. 2, the estimated locations (red squares) of patient Y were superimposed on MR images scanned by an image scanner controlled by the DT method. The spatial matching between MR and DT images was performed by adjusting the slice levels and the outermost out-lines of the horizontal sections of both images. It is clear from Fig. 2 that the generators of the interictal spikes were located in the right hippocampal region. 3. Three-dimensional display' of spike generators. The dipole locations were three-dimensionally displayed with yellow balls in a expanded space in two patients H and Y as shown in Fig. 3. As can be seen in Fig. 3, the locations of the spike
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Fig. 2. Estimated locations (red squares) superimposed on three different slice levels (5 mm intervals) of MRI of the patient Y. Fig. 3. Three-dimensional display of spike generators (yellow balls) in the patient H (upper half) and Y (lower half). Red rhombi indicate the position of active surfaces of the depth electrode. A, anterior; P, posterior.
172
generator seem to be composed of two structures (upper and lower ones) and to show trail-like tubules in the parahippocampal and hippocampal regions in two cases. 4. Generator mechanisms of spike potentials. It was assumed in a hippocampal neuron that a current flows in at synapses on the apical dendrite and flows out from the soma, thus composing a current dipole, and that synchronous activity of many neurons is detected as a potential. The present DT method assumes such synchronous activity of many neurons as an equivalent single dipole and estimates the location and vector moment of the dipole using inverse solution of actually recorded potentials. As shown in Fig. 3, the dipole locations successively moved in a small limited region and the vectors were uni-directional during the spike's peak. These findings seem to indicate that an interictal spike is composed of several equivalent current dipoles which are summated, and that each equivalent dipole is generated by hypersynchronization of a cluster of neurons as suggested by Engel [2], but that the timing of such hyperexcitation due to compensatory axonal sproutings in each neuronal cluster is more or less delayed because of electrical propagation along neuronal cluster arrangement which might be separated by sclerotic tissues. It was supposed that the structure like trailing tubule seen in Fig. 3 might correspond with abnormal neural architecture of the hippocampus or parahippocampus with epileptic focus. But
the mechanisms how interictal spikes, generated in such an abnormal neuronal architecture, develop into an epileptic state were not clarified in the present study. We deeply express our thanks to Dr. M. Seino, Director and Dr. Y. Watanabe of Shizuoka Higashi National Hospital, for their kind contribution to our research program. 1 De Munck, J.C., Van Dijk, B.W. and Spekreijse, H., Mathematical dipoles are adequate to describe realistic generators of human brain activity, IEEE Trans. Biomed. Eng., BME-35 (1988) 960-966. 2 Engel Jr., J., Functional explorations of the human epileptic brain and their thrapeutic implications, Electroencephalogr. Clin. Neurophysiol., 76 (1990) 29(~316. 3 He, B., Musha, T., Okamoto, Y., Homma, S., Nakajima, Y. and Sato, T., Electric dipole tracing in the brain by means of the boundary element method and its accuracy, IEEE Trans. Biomed. Eng., BME-34 (1987) 406-414. 4 He, B., Okamoto, Y., Musha, T., Nakajima, Y. and Homma, S., Evaluation of errors in estimating an electric dipole in the brain, Jpn. J. Med. Electron. Biol. Eng., 24 (1986) 315-320 (in Japanese). 5 Homma, S., Nakajima, Y., Musha, T., Okamoto, Y. and He, B., Dipole-tracing analysis applied to human brain potentials, J. Neurosci. Methods, 21 (1987) 195 200. 6 Homma, S., Nakajima, Y., Musha, T., Okamoto, Y., Hagbarth, K.-E., Blom, S. and Flink, R., Generator mechanisms of epileptic potentials analyzed by dipole tracing method, Neurosci. Lett., 113 (1990) 181 186. 7 Wood, C.C., Application of dipole localization methods to human evoked potentials, Ann NY Acad. Sci., 388 (1982) 139 155.
169
NSL 08429
Estimation of neural architecture in human brain by means of the dipole tracing method Yoshio N a k a j i m a a, Saburo H o m m a a, Toshimitsu M u s h a b, Hiroshi Sasaki b and Yoshiwo O k a m o t o c ODepartment of Physiology, School of Medicine, Chiba University, Chiba (Japan), bDepartmentof Applied Electronics, Tokyo Institute of Technology, Yokohama (Japan) and CDepartmentof Electronics, Chiba Institute of Technology, Chiba (Japan) (Received 12 November 1991; Accepted 27 November 1991)
Key words: Dipole tracing; Depth electrode; Epileptic spike; Hippocampus; Neural structure The electric source locations of interictal spikes recorded with depth electrodes were estimated by the dipole tracing (DT) method. Threedimensional coordinates of the active surfaces of the depth electrodes and head geometry of the patient were measured from frontal and saggital X-ray images and by a special device, respectively. The estimated dipole locations were superimposed on MR images of the patients. The dipole locations estimated in the hippocampal or parahipocampal regions successively moved in a small limited region during the interictal spike's peak. It was suggested that an interictal spike is composed of summated equivalent dipoles generated by hypersynchronization of a cluster of neurons, and that the timing of such hyperexcitation is more or less delayed because of electrical propagation along neuronal clusters which might be separated by sclerotic tissues.
To estimate the location of an electric source generator (e.g. a current dipole) within the human brain, a new computer-aided method was developed [3, 5]. Activity of neural structures in a region of the brain was represented as one equivalent current dipole [1, 7]. This method, which is called dipole tracing (DT), enables one to estimate the locations and vector moments of such dipoles. To estimate the electric location of interictal spikes recorded from patients with electrodes inserted into the brain, a head model with an infinite and homogeneous conductivity was assumed in forward solution. Dipolarity of more than 98%, which indicates the accuracy of estimation as an equivalent current dipole [4], was adopted as being significant since such high dipolarity is assumed that the estimated dipole location and vector moment correspond with true ones [6]. The present study was performed after obtaining the informed consent from two patients with epilepsy at the National Epilepsy Center, Shizuoka Higashi Hospital, for neurological treatment. Four to 5 depth electrodes, each of which has 5 active surfaces at 5 mm intervals, were inserted into the brain approximately 1 week prior to EEG recordings. Interictal spikes were monopolarly and simultaneouly recorded with 19 out of 20 or 25 acCorrespondence: Y. Nakajima, Department of Physiology, School of Medicine, Chiba University, 1 8-1, Inohana, Chiba 280, Japan. Fax: (81) 472-22 7853.
tive surfaces. The interictal spikes thus recorded were analyzed using the DT method. 1. Three-dimensional coordinates of depth electrodes inserted in to the brain and the head geometry. Three-dimensional coordinates of the active surfaces of the depth electrodes were measured from frontal and saggital X-ray images taken during stereotactic surgical operation and by parallel X-ray irradiation. The reference point for coordinate measurement was set at the center of four stereotactic fixation points of the scalp which were set in parallel to the OM-line of the patient. The head geometry of a patient was measured by a specially designed device prior to surgical operation. The device was made of a semi-spherical helmet with 64 displacement sensors, by which three-dimensional coordinates of the tips of the sensors (that correspond with coordinates of outer surface of the head) were measured from a patient. The OM-line and mid-line of the helmet were adjusted to correspond with those of the patient prior to measurement. In Fig. 1A, the spatial relationships between the outermost out-line of the head measured by the device and the nineteen active surfaces of depth electrodes measured from X-ray images are shown on the horizontal sections of two patients, H and Y. The electrode positions, from which interictal spikes are actually recorded, are shown as open circles. 2. Dipole tracing of interictal spikes. As can be seen in
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Fig. 1. A: interictal spikes simultaneously recorded with depth electrodes indicated by open circles are shown in the horizontal section of the head in two patients H and Y. Estimated locations of the spike generator are also indicated by filled circles in the respective patient. B: estimated locations and vector moments on the three plains of the head of patient Y. PH, parahippocampus; H, hippocampus; A, amygdala; OF, orbitofrontal.
Fig. 1A (patient H), interictal spikes were recorded with high amplitude from the depth electrodes H and PH inserted into the left hippocampus and parahippocampus, respectively. Furthermore, the phase reversal was observed between electrode Nos. 2 and 3 of the depth electrode PH. (cf., The smaller the electrode number, the more medially the active surface is located.) These findings indicate that the generator of the spike lies between electrode Nos. 2 and 3 of the depth electrode PH. From the 19 recordings, the location of the spike generator was estimated by the DT method and the result is shown by filled circles in the horizontal section in Fig. 1A (left). The generator of the spike is estimated in the vicinity of electrode No. 3, between electrode Nos. 2 and 3. In the case of patient Y (right side of Fig. 1A), the high amplitude spike is selectively recorded from the depth electrode H inserted into the right hippocampus although the phase reversal was not clearly observed. The location of the spike generator estimated by the DT method is shown as filled circles in the horizontal section of patient H. In this case, the generator was estimated in the vicinity of electrode No. 2 of the depth electrode H. Fig. 1B shows the spatial relationship of the position
of the active surfaces, dipole locations and vector moments in horizontal, frontal and saggital sections of patient Y. The dipole locations and vector moments shown in Fig. 1B were calculated at 5 ms intervals around the interictal spike's peak. As can be seen in Fig. 1B, all of the estimated vectors were similarly directed. Four to 5 dipoles were estimated from a single spike of patient Y and they moved temporally and spatially within a narrow space. As can be seen in Fig. 2, the estimated locations (red squares) of patient Y were superimposed on MR images scanned by an image scanner controlled by the DT method. The spatial matching between MR and DT images was performed by adjusting the slice levels and the outermost out-lines of the horizontal sections of both images. It is clear from Fig. 2 that the generators of the interictal spikes were located in the right hippocampal region. 3. Three-dimensional display' of spike generators. The dipole locations were three-dimensionally displayed with yellow balls in a expanded space in two patients H and Y as shown in Fig. 3. As can be seen in Fig. 3, the locations of the spike
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Fig. 2. Estimated locations (red squares) superimposed on three different slice levels (5 mm intervals) of MRI of the patient Y. Fig. 3. Three-dimensional display of spike generators (yellow balls) in the patient H (upper half) and Y (lower half). Red rhombi indicate the position of active surfaces of the depth electrode. A, anterior; P, posterior.
172
generator seem to be composed of two structures (upper and lower ones) and to show trail-like tubules in the parahippocampal and hippocampal regions in two cases. 4. Generator mechanisms of spike potentials. It was assumed in a hippocampal neuron that a current flows in at synapses on the apical dendrite and flows out from the soma, thus composing a current dipole, and that synchronous activity of many neurons is detected as a potential. The present DT method assumes such synchronous activity of many neurons as an equivalent single dipole and estimates the location and vector moment of the dipole using inverse solution of actually recorded potentials. As shown in Fig. 3, the dipole locations successively moved in a small limited region and the vectors were uni-directional during the spike's peak. These findings seem to indicate that an interictal spike is composed of several equivalent current dipoles which are summated, and that each equivalent dipole is generated by hypersynchronization of a cluster of neurons as suggested by Engel [2], but that the timing of such hyperexcitation due to compensatory axonal sproutings in each neuronal cluster is more or less delayed because of electrical propagation along neuronal cluster arrangement which might be separated by sclerotic tissues. It was supposed that the structure like trailing tubule seen in Fig. 3 might correspond with abnormal neural architecture of the hippocampus or parahippocampus with epileptic focus. But
the mechanisms how interictal spikes, generated in such an abnormal neuronal architecture, develop into an epileptic state were not clarified in the present study. We deeply express our thanks to Dr. M. Seino, Director and Dr. Y. Watanabe of Shizuoka Higashi National Hospital, for their kind contribution to our research program. 1 De Munck, J.C., Van Dijk, B.W. and Spekreijse, H., Mathematical dipoles are adequate to describe realistic generators of human brain activity, IEEE Trans. Biomed. Eng., BME-35 (1988) 960-966. 2 Engel Jr., J., Functional explorations of the human epileptic brain and their thrapeutic implications, Electroencephalogr. Clin. Neurophysiol., 76 (1990) 29(~316. 3 He, B., Musha, T., Okamoto, Y., Homma, S., Nakajima, Y. and Sato, T., Electric dipole tracing in the brain by means of the boundary element method and its accuracy, IEEE Trans. Biomed. Eng., BME-34 (1987) 406-414. 4 He, B., Okamoto, Y., Musha, T., Nakajima, Y. and Homma, S., Evaluation of errors in estimating an electric dipole in the brain, Jpn. J. Med. Electron. Biol. Eng., 24 (1986) 315-320 (in Japanese). 5 Homma, S., Nakajima, Y., Musha, T., Okamoto, Y. and He, B., Dipole-tracing analysis applied to human brain potentials, J. Neurosci. Methods, 21 (1987) 195 200. 6 Homma, S., Nakajima, Y., Musha, T., Okamoto, Y., Hagbarth, K.-E., Blom, S. and Flink, R., Generator mechanisms of epileptic potentials analyzed by dipole tracing method, Neurosci. Lett., 113 (1990) 181 186. 7 Wood, C.C., Application of dipole localization methods to human evoked potentials, Ann NY Acad. Sci., 388 (1982) 139 155.