Chloralose

Coupling of neuronal activity to cerebral blood flow (CBF) is widely accepted, but the exact mechanism is still under investigation. We assessed the responses of CBF coupled with electrical activity over the primary somatosensory cortex (S-I) during electrical stimulation of the contralateral forearm in cats. CBF in S-I was monitored using laser-Doppler flowmetry (LDF), and electrical activity was recorded with a tungsten microelectrode. The effects of varying stimulus intensity and frequency were examined to assess the optimal stimulation parameters. CBF increased within 10 sec after onset of stimulation, sustained the plateau level, and returned to the pre-stimulus level after cessation of stimulation. The maximum response was obtained at 4 Hz under a constant intensity. Optimal stimulus intensity at 4 Hz ranged from 8 to 10 V. At intensity higher than 10 V, CBF increases reached a near-plateau level, while mean arterial blood pressure (MABP) decreased slightly. Electrical activity was recorded at the same restricted area where CBF increased. Low frequency components of the power spectrum of electrical activity increased as the CBF increase became greater. A tight coupling of CBF increases to neuronal activation is suggested, and CBF regulation may be affected by stimulation parameters. [Neurol Res 1999; 21: 579-584]

Keywords: Cerebral blood flow; electrical activity; electrical stimulation; laser-Doppler flowmetry; primary somatosensory cortex; regulation

INTRODUCTION

It is widely accepted that cerebral blood flow (CBF) is tightly coupled to brain function. Various investigations have shown these CBF changes under neuronal activation in humans and animals.1-7 However, responses of CBF regulation to various neuronal activations are still under investigation, and the exact mechanisms underlying the coupling of CBF and neuronal activity are still unknown. Kuchiwaki et al.8 showed that blocking in ATP production lowered both CBF levels and electrical brain activity, and suggested that the brain metabolism is an important factor for CBF regulation. In our present study, we investigated the relationship between CBF regulation and brain electrical activity in the primary somatosensory cortex (S-I) during electrical stimulation of the forearm in cats utilizing laser-Doppler flowmetry (LDF) and an extracellular microelectrode. We hypothesized that maximum response of CBF increases in S-I may be induced by the optimum electrical stimulus.

MATERIALS AND METHODS

Animal preparation

Ten adult cats of both sexes weighing 2.6-4.7 kg were used in the study under the animal experimentation guidelines of Nagoya University School of Medicine. Anesthesia was induced with ketamine hydrochloride (20 mg kg^sup -1^, i.m.), then maintained with alpha-chloralose and urethane (30 and 150 mg kg^sup -1^ , respectively, i.v.). The animals were tracheotomized, immobilized with pancuronium bromide (0.5 mg kg^sup -1^, i.v.), and mechanically ventilated with room air. Additional chloralose (10 mg kg^sup -1^, i.v.), urethane (50 mg kg^sup -1^, i.v.), and pancuronium (0.25 mg kg^sup -1^, i.v.) were given hourly for anesthesia and paralysis. End-expiratory CO2 was continuously monitored with a CO2 analyzer (model 1H21A; San-ei Instrument Co., Tokyo, Japan) and maintained at 4.8-5.1%. The left femoral artery and vein were cannulated for monitoring blood pressure (BP), blood gas sampling, and drug administration. Rectal temperature was maintained at 37 deg C by a heating pad. The animals were secured in a stereotactic frame (Narishige Inc., Tokyo, Japan).

After unilateral frontoparietal craniectomy, the dura mater was removed from S-I. According to the method proposed by Kimura and Tamai9, a round acrylic chamber enclosing the bone defect was attached to the skull with dental cement. The chamber was filled with warm liquid paraffin, and a cover glass 1 mm thick with a 2 mm diameter hole was placed on the chamber. The cisterna magna was opened to drain cerebrospinal fluid. These procedures effectively reduced cardiac and respiratory pulsations of the cortex, and thus ensured stability of the recordings.

CBF measurement

CBF was monitored continuously using LDF. The flowmeter (model ALF2100; Advance Co., Tokyo, Japan) had a He-Ne laser beam with an optical output power of 2 mW and a wavelength of 632.8 nm. A needle type probe 1 mm in diameter mounted on a stereotactic manipulator was inserted through a hole in the cover glass on the cranial window, and placed perpendicularly on the forearm area of S-I according to the somatotopic maps10. The gap between the probe and the hole was packed with petroleum jelly. Care was taken not to place the probe above large pial vessels. The time constant was set at 1.0 sec.

Estimation and activation of S-I by electrical stimulation

S-I was activated by electrical stimulation of the contralateral forearm with two needle electrodes introduced into the subcutaneous tissue. The electrodes were stimulated by a stimulus isolation unit (model SS-101J; Nihon Kohden Co., Tokyo, Japan) that was in turn driven by an electronic stimulator (model SEN-1101; Nihon Kohden Co.). The corresponding receptive fields of the forearm were localized by searching points of maximal CBF response by slightly shifting the electrode positions.

The effects of varying stimulus intensity and frequency were examined in six animals to assess the optimal stimulation parameters. Rectangular positive pulses of 0.3 msec duration, 1-30V intensity, and 2-20 Hz frequency were applied as stimulations. The stimulation was given for 30 sec. It was repeated three times in each parameter to obtain mean response values. The interval between each stimulation was 5 min, or more if CBF had not normalized. The total experimental times did not exceed 4 h.

Extracellular sampling of neuronal activity at electrical stimulation

Extracellular recordings in S-I were performed in four animals to verify neuronal activation. Electrical activities were recorded with a tungsten microelectrode (impedance 2.0 M(Omega) at 1 kHz; model OH96-029; Unique Medical Co., Tokyo, Japan) which was mounted on a stereotactic manipulator. The closed cranial window technique was also utilized. The electrode was placed into the same area where maximal CBF increase by electrical stimulation had been obtained. The tip of the electrode was advanced up to 1 mm below the cortical surface.

The contralateral forearm was stimulated with varying parameters. The signals were amplified with a biophysical amplifier (model DPA-000; DIA-Medical System Co., Tokyo, Japan). The low-pass filter was set to 10 kHz, and the high-pass filter was set to 1 Hz to remove the DC-offset. The amplifier output was displayed on an oscilloscope (model 5103N; Tektronix Inc., Wilsonville, OR, USA), and also passed to an audio amplifier and a loudspeaker. These data were stored in analog tape using a cassette data recorder (model R-80; TEAC Corp., Tokyo, Japan), and processed off-line by a computer system.

Data analysis

CBF increases to electrical stimulation were calculated as a percentage of the maximal value to the prestimulus one. All values are expressed as means +/- SD. Statistical comparisons were performed using one-way repeated-measures analysis of variance (ANOVA). A p value of 0.05 or less was considered significant.

Fast Fourier transform (FFT) was applied to electrical activity through power spectrum analysis in the frequencies 2-64 Hz. Signals after stimulation were analyzed for 100 msec.

RESULTS

Physiological variables

The physiological variables at resting conditions for all animals (n=lO) were as follows: mean arterial blood pressure (MABP), 129 +/- 12 mmHg; pH, 7.39 +/- 0.07; pCO2, 34.3 +/- 4.7 mmHg; and pO2, 102.2 +/- 13.6 mmHg. These values were maintained throughout each experiment.

Time courses of CBF and BP response

A representative example of CBF and BP changes was shown in Figure 1. Electrical stimulation of the forearm induced the highest increase in CBF on the contralateral corresponding area of S-I. The increase was strictly confined to the forearm area of 1-2 mm in diameter. An increase in CBF started within 24 sec after onset of stimulation, reached a maximal value within 10 sec, and subsequently declined to a plateau that persisted for the rest of the stimulus period. After cessation of stimulation, CBF gradually returned to the pre-stimulus level within 10 sec. In some of the post-stimulus period, CBF fell below baseline for 30-45 sec but returned to the prestimulus level within 1-2 min.

In contrast, BP decreased during stimulation. Decreases in BP started within 3-6 sec after onset of stimulation, and smoothly reached a minimal value that persisted during the stimulation. After cessation of stimulation, BP recovered to the pre-stimulus level.

Effect of intensity changes under constant frequency

Figure 2A illustrates an example of the effect of altering stimulus intensity on CBF and BP under a constant frequency of 4 Hz. In general, the increase of CBF was stronger as the stimulus intensity became higher up to 10V. As illustrated in Figure 3A, when stimulus intensity was increased from 1 to 10 V, there was a rapid increase in CBF response. At 1 V, CBF increase was not obtained in 4 of 6 animals. The mean percentage CBF with parameters of 10 V and 4 Hz was 116.6 +/- 3.2%. At an intensity of 10 V or more, CBF increases reached a near-plateau level.

In contrast, MABP decreased more as the intensity became higher (Figures 2A and 3B). The mean percentage MABP at 10 V and 4 Hz was 96.1 +/- 0.6%. At voltages of 4 or less, no depressor effect was noted.

Effect of frequency chan es under constant intensity

Figure 2B shows an example of the effect of altering stimulus frequency on CBF and BP under 8 V. The maximal response occurred at 4 Hz stimulation. As indicated in Figure 3C, when the frequency was increased to 4 Hz, there was a marked increase in CBF response. Further increasing of frequency reduced degrees of CBF increases. In contrast, frequency changes had no significant effect on the levels of MABP (Figures 2B and 3D) (F=0.933, p=0.5118).

Signal processing of extracellular potentials

Figure 4 gives an example of the recording of extracellular potentials in S-I. Electrical stimulation produced a short burst of neuronal activity localized to the forearm area of S-I. The latency of electrical activity was approximately 20 msec after the stimulation, and showed a similar pattern by the changes in intensity or frequency of the stimulation. However, amplitudes of electrical activity from the highest to the lowest peak were maximal at an intensity of more than 10 V and a frequency of 4 Hz.

Figure 5 indicates a power spectrum analysis of the electrical activity at different stimulus parameters. In Figure SA, the stimulus frequency was kept constant at 4 Hz. When stimulus intensity was increased from 1 to 10 V, there was a relative increase in the low frequency components with a two-peak pattern (6-8 and 13-- 15Hz). At a stimulus intensity higher than 10V, the powers above low components were similar to those at 10 V. In Figure SB, the stimulus intensity was kept constant at 8 V. The powers above low components were maximal at 4 Hz stimulation. This power spectrum pattern disappeared by increasing the frequency.

When calculated at a low frequency ranging from 615 Hz, the percentage power changed by electrical stimulation at different stimulus parameters (Figure 6). The percentage power in changing intensities tended to increase up to 8 V and then a plateau level (Figure 6A). On the other hand, the percentage power in changing frequencies showed a peak at 4 Hz (Figure 6B). Although these changes of percentage power were not statistically significant, in response to both intensity and frequency changes (F = 1.834, p= 0.0652, and F=2.104, p=0.0565, respectively), the changing patterns were similar to those in responses of CBF (Figures 3A and 6A, Figures 3C and 6B, respectively).

DISCUSSION

Our results indicated that electrical stimulation could induce increases in neuronal activity and CBF in the restricted area of S-I. The degrees of CBF increase and neuronal activation were definitely dependent on those of stimulation parameters.

LDF

In the present study, we monitored CBF responses utilizing LDF. LDF is a non-invasive technique for assessment of CBF, and has advantages of real-time monitoring11-17. Its validity for studies of brain circulation has been established in several studies using the hydrogen clearance technique15,18-21, microspheres11,22-24, pial artery diameter20,25, and [^sup 14^C]iodoantipyrine (IAP)17,26,27. However, the LDF signal does not provide absolute CBF values17,26,28 Thus, we assessed CBF responses to stimulation as percentage changes from pre-stimulus levels.

Pattern of CBF increase

We showed that CBF increased rapidly at maximum levels within 10 sec after onset of stimulation, remained on a plateau for the rest of the stimulus period, and then returned to the pre-stimulus level after cessation of stimulation. This time course compares with that of other investigators. Ngai et al5 recorded LDF responses to sciatic nerve stimulation in rats and demonstrated a similar time course. In contrast, Leniger-Follert and Hossmann1, who analyzed CBF responses in cats utilizing the local hydrogen clearance method, stated that maximum flow was reached only at the end of the stimulation period. These discrepancies may be explained by the recording techniques, the anesthetic agents used, and the degree of anesthesia.

Effect of stimulus intensity changes

When we increased stimulus intensity from 1 to 10 V, there was a rapid increase in CBF response. Beyond 10 V, however, the response drew near its plateau level. It is thought that as the stimulation of a peripheral nerve is increased in intensity, larger fibers (A-delta) are activated before smaller fibers (C) when the animals are anesthetized by chloralose and paralyzed29, and that only the larger fibers are necessary to elicit a maximal CBF increase in S-I30.

A plateau in responses at higher intensity may be explained from the depressor effects on MABP during stimulation. In the present study, no change in MABP occurred during lower voltage stimulation than 4V. However, during higher intensities, all animals showed a slight lowering of MABP, and its levels reduced as stimulus intensity increased. As cerebral autoregulation may not be a process rapid enough to compensate for this MABP reduction31, CBF increase may be limited by the inhibition mechanism. This depressor effect in MABP, which is similar to that of Leniger-Follert and Hossmann1, is considered to be elicited by vasomotor reflex32, and change in MABP is thought to depend on which peripheral nerve fibers are activated29,30,32,33. It may be that this depressor response in MABP affects the time course of CBF increases as we noted above, and confounds data interpretation. Thus, we chose the optimal stimulus intensity as 8-10 V because of the consistency of maximal response in CBF increases and small effect on MABP reduction.

Effect of stimulus frequency changes

The effect of changes in stimulus frequency in our study contrasts with that of other investigators. Ngai et al.5,30 showed that maximum dilation of pial arteriolar diameter and CBF increase were attained at a frequency of 5 Hz, but with significant attenuation when frequency was increased beyond 10 Hz. Leniger-Follert and Hossmann' stated that the maximum CBF increase was obtained at 2-3 Hz. Tsubokawa et al.2 studied CBF responses to sciatic nerve stimulation in cats utilizing the hydrogen clearance method, and noted that maximum flow in S-I was obtained at 10 Hz. Different results in these authors may also be explained by differences in experimental protocols.

CBF increases responding to changes in frequencies of the various kinds of stimuli have also been investigated in humans by several investigators. Using positron emission tomography (PET) and ^sup 15^O-labeled water, Sadato et al.6 estimated the effect of movement repetition rate on the distribution and magnitude of CBF changes in healthy subjects who performed simple repetitive finger movements (sensorimotor stimulation) with a wide range of rates (0.25-4 Hz) strictly controlled by an external auditory cue. There was a rapid rise of CBF with the rates between 0.75 and 2.5 Hz, but no further increase at faster rates. Apkarian et al.34 showed that sustained pain perception due to thermal stimulation (noxious stimulation) was accompanied by decreased contralateral parietal CBF within and around the S-I. Intracortical inhibition is considered one of the mechanisms of this frequency-dependent response30,34,35. Another possibility is that the refractory phase between sensory stimuli may be involved in the attenuation of CBF increases. Habituation of the cortical cells to higher stimulus frequency should also be considered a mechanism possibly involved.

Coupling of neuronal activity to CBF

The cortical cells in S-I were definitely activated electrically during stimulation at the same restricted area where CBF increase could be observed by LDF. Neuronal activation was obtained within 20 msec after the onset of stimulation, which was similar to a previous observation36.

When percentage of total power within the low (6-- 15 Hz) frequency band was calculated, the changes in it caused by varying stimulus parameters were correlated well with those of CBF. This coupling between CBF and relatively lower frequency band in neuronal activity has not been reported previously. Based on the theory of shifts in frequency-tuning curves of neurons in the corticofugal auditory system37, electrical stimulation which induces CBF increase may activate more neurons in S-I tuned to lower rather than higher frequencies. As a result, the power spectrum pattern can shift to lower frequencies.

The mechanisms evoking a tight coupling of neuronal activity to CBF have not yet been clarified. The metabolic mechanisms initially proposed by Roy and Sherrington38 have been considered to explain the coupling. Several authors of the present study conducted an experiment in which CBF was found to decrease due to intravenous injection of an agent of blocking ATP production8, thus supporting the metabolic mechanism. In contrast, Ogawa et al.39, using PET in cats, showed that scopolamine abolished the CBF response to stimulation, and suggested an important role of the neurogenic mechanisms proposed earlier by Lou et al.40. Lindauer et al.41 investigated the CBF response to whisker deflection in rats with LDF, and obtained a similar pattern of response to our study. They proposed that the neurogenic mechanism may be responsible for the rapid onset of the CBF response, and the following plateau response may mainly be the result of the metabolic mechanism.

In the present study, we did not examine the metabolic factors eliciting CBF response to stimulation. Further studies need to clarify the mechanisms of CBF regulation under neuronal activation.

In conclusion, this study shows that optimal stimulus parameters exist to obtain maximal increases in CBF and neuronal activity, while MABP decreases slightly. These findings may become clues to clarify the mechanism of coupling of neuronal activity to CBF, and that of sensory transmission in neurological disorders.

ACKNOWLEDGEMENTS

The authors thank Yasuhiko Tamai, MD, Department of Physiology, Wakayama Medical College, for invaluable assistance in the closed cranial window technique. The authors are also grateful to Hirokazu Iguchi, PhD, Toyota Central Institute Inc., for computerized data analysis.

REFERENCES

1 Leniger-Follert E, Hossmann K-A. Simultaneous measurements of microflow and evoked potentials in the somatomotor cortex of the cat brain during specific sensory activation. Pflugers Arch 1979; 380: 85-89

2 Tsubokawa T, Katayama Y, Kondo T, Ueno Y, Hayashi N, Moriyasu N. Chan es in local cerebral blood flow and neuronal activity

during sensory stimulation in normal and sympathectomized cats. Brain Res 1980;190: 51-65

3Fox PT, Raichle ME. Stimulus rate dependence of regional cerebral blood flow in human striate cortex, demonstrated by positron emission tomography. J Neurophysiol 1984; 51: 1109-1120

4 Phelps ME, Mazziotta JC. Positron emission tomography: Human brain function and biochemistry. Science 1985; 228: 799-809

5 Ngai AC, Meno JR, Winn HR. Simultaneous measurements of pial arteriolar diameter and laser-Doppler flow during somatosensory stimulation. J Cereb Blood Flow Metab 1995; 15: 124127

6 Sadato N, Ibanez V, Deiber MP, Campbell G, Leonardo M, Hallett M. Frequency-dependent changes of regional cerebral blood flow during finger movements. J Cereb Blood Flow Metab 1996; 16: 23-33

7 Rao SM, Bandettini PA, Binder JR, Bobholz JA, Hammeke TA, Stein EA, Hyde IS. Relationship between finger movement rate and

functional magnetic resonance signal change in human primary motor cortex. J Cereb Blood Flow Metab 1996; 16:1250-1254

8 Kuchiwaki H, Inao S, Yoshida K, Sugita K. Effect of intracarotid administration of 6-aminonicotinamide on cerebral blood flow in cats. Stroke 1995; 26: 473479

9 Kimura A, Tamai Y. Sensory response of cortical neurons in the anterior ectosylvian sulcus, including the area evoking eye movement. Brain Res 1992; 575: 181-186

10 Felleman DJ, Wall JT, Cusick CG, Kaas JH. The representation of the body surface in S-I of cats. J Neurosci 1983; 3: 1648-1669

11 Eyre JA, Essex TJ, Flecknell PA, Bartholomew PH, Sinclair JI. A comparison of measurements of cerebral blood flow in the rabbit using laser Doppler spectroscopy and radionuclide labelled microspheres. Clin Phys Physiol Meas 1988; 9: 65-74

12 Kocher M. Metabolic and hemodynamic activation of postischemic rat brain by cortical spreading depression. J Cereb Blood Flow Metab 1990;10: 564-571

13 Carter LP. Surface monitoring of cerebral cortical blood flow. Cerebrovasc Brain Metab Rev 1991; 3: 246-261

14 Piper RD, Lambert GA, Duckworth JW. Cortical blood flow changes during spreading depression in cats. Am J Physiol 1991; 261: H96-H102

15 nao S, Kuchiwaki H, Sugita K. Microcirculation in experimental brain oedema assessed by laser-Doppler flowmetry. Neurol Res

1993; 15: 264-268

16 Morita-Tsuzuki Y, Hardebo JE, Bouskela E. Interaction between cerebrovascular sympathetic, parasympathetic and sensory nerves in blood flow regulation. J Vasc Res 1993; 30: 263-271

17 Fabricius M, Lauritzen M. Laser-Doppler evaluation of rat brain microcirculation: Comparison with the [14C]-Iodoantipyrine method suggests discordance during cerebral blood flow increases. J Cereb Blood Flow Metab 1996;16: 156-161

18 DiResta GR, Arbit E, Lau N, Galicich JH. Measurement of regional cerebral blood flow using a combination laser Doppler-hydrogen clearance probe. J Cereb Blood Flow Metab 1987; 1 (Suppl. 7): S570

19 Skarphedinsson JO, Harding H, Thoren P. Repeated measurements of cerebral blood flow in rats. Comparisons between the hydrogen clearance method and laser Doppler flowmetry. Acta Physiol Scand 1988; 134: 133-142

20 Haberl RL, Heizer ML, Marmarou A, Ellis EF. Laser-Doppler assessment of brain microcirculation: Effect of systemic alterations. Am J Physiol 1989; 256: H1247-H1254

21 Kuchiwaki H, Inao S, Sugita K, Kashima S. An experimental study of cerebral blood flow and some considerations on obtaining reliable data using a laser flow meter. Laser Therapy 1991; 3: 51-57

22 Lindsberg PJ, O'Neill JT, Paakkari IA, Hallenbeck JM, Feuerstein G. Validation of laser-Doppler flowmetry in measurement of spinal

cord blood flow. Am J Physiol 1989; 257: H674H680

23 Talman WT, Dragon DM, Heistad DD, Ohta H. Cerebrovascular effects produced by electrical stimulation of fastigial nucleus. Am J Physiol 1991; 261: H707-H713

24 Colditz PB, Bartholomew PH, Sinclair Jl, Murphy D, Rolfe P, Wilkinson AR. Electrical impedance plethysmography: Its use in studying the cerebral circulation of the rabbit. Med Biol Eng Comput 1993; 31: 39-42

25 Haberl RL, Heizer ML, Ellis EF. Laser-Doppler assessment of brain microcirculation: Effect of local alterations. Am I PhYsiol 1989;

256: H1255-H1260

26 Dirnagl U, Kaplan B, Jacewicz M, Pulsinelli W. Continuous measurement of cerebral cortical blood flow by laser-Doppler flowmetry in a rat stroke model. J Cereb Blood Flow Metab 1989; 9: 589-596

27 Goadsby PJ. Characteristics of facial nerve-elicited cerebral vasodilation determined using laser Doppler flowmetry. Am J

Physiol 1991; 260: R255-R262

28 Kramer MS, Vinall PE, Katolik LI, Simeone FA. Comparison of cerebral blood flow measured by laser-Doppler flowmetry and hydrogen clearance in cats after cerebral insult and hypervolemic hemodilution. Neurosurgery 1996; 38: 355-361

29 Shyu BC, Andersson SA, Thoren P. Circulatory depression following low frequency stimulation of the sciatic nerve in anesthetized rats. Acta Physiol Scand 1984;121: 97-102

30 Ngai AC, Ko KR, Mor S, Winn HR. Effect of sciatic nerve stimulation on pial arterioles in rats. Am J Physiol 1988; 254: H133-H139

31 Florence G, Seylaz J. Rapid autoregulation of cerebral blood flow: A laser-Doppler flowmetry study. I Cereb Blood Flow Metab 1992;

12: 674-680

32 Skoglund CR. Vasomotor reflexes from muscle. Acta Physiol Scand 1960; 50: 311-327

33 Johansson B. Circulatory responses to stimulation of somatic afferents. Acta Physiol Scand 1962; 57 (Suppl. 198): 1-91

34 Apkarian AV, Stea RA, Manglos SH, Szeverenyi NM, King RB, Thomas FD. Persistent pain inhibits contralateral somatosensory cortical activity in humans. Neurosci Lett 1992; 140:141-147

35 Hellweg FC, Schultz W, Creutzfeldt OD. Extracellular and intracellular recordings from cat's cortical whisker projection area: Thalamocortical response transformation. J Neurophysiol 1977; 40: 463-479

36 Narayan SM, Esfahani P, Blood AJ, Sikkens L, Toga AW. Functional increases in cerebral blood volume over somatosensory cortex.

J Cereb Blood Flow Metab 1995;15: 754-765

37 Yan W, Suga N. Corticofugal modulation of the midbrain frequency map in the bat auditory system. Nature Neurosci 1998; 1: 54-58

38 Roy CW, Sherrington CS. On the regulation of the blood supply of the brain. J Physiol 1890; 11: 85-108

39 Ogawa M, Magata Y, Ouchi Y, Fukuyama H, Yamauchi H, Kimura

J, Yonekura Y, Konishi J. Scopolamine abolishes cerebral blood flow response to somatosensory stimulation in anesthetized cats: PET study. Brain Res 1994; 650: 249-252

40 Lou HC, Edvinsson L, MacKenzie ET. The concept of coupling blood flow to brain function: Revision required? Ann Neurol 1987; 22: 289-297

41 Lindauer U, Villringer A, Dirnagl U. Characterization of CBF response to somatosensory stimulation: Model and influence of anesthetics. Am J Physiol 1993; 264: H1223-H1228

Kazuyoshi Ichimi, Hiroji Kuchiwaki, Suguru Inao, Mikine Shibayama and Jun Yoshida

Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan

Correspondence and reprint requests to: Kazuyoshi Ichimi, MD, Department of Neurosurgery, Nakatsugawa Municipal General Hospital, 1522-1 Komanba, Nakatsugawa, Gifu 508-8502, Japan. Accepted for publication April 1999.

Copyright Forefront Publishing Group Sep 1999
Provided by ProQuest Information and Learning Company. All rights Reserved