- Email: [email protected]
Pain-related cerebral potentials in patients with frontal or parietal lobe lesions
ELSEVIER
Neuroscience Letters 197 (1995) 137-140
NEUROSCIENCE LETT[IS
Pain-related cerebral potentials in patients with frontal or parietal lobe lesions Irene Daum",*, Christoph Braun", Gerlinde Riesch a, Wolfgang Miltner b, Hermann Ackermann c, Markus M. Schugens,, Niels Birbaumer a alnstitute of Medical Psychology and Behavioral Neurobiology, University of Ti~'bingen, Gartenstrasse 29, 72074 Tiibingen, Germany blnstitute of Psychology, University of Jena, Jena, Germany CDepartment of Neurology, University of Tiibingen, Tiibingen, Germany
Received 30 June 1995; revised version received 7 August 1995; accepted 7 August 1995
Abstract The present study investigated the processing of painful electrical stimuli in patients with unilateral frontal or parietal lobe damage and matched control subjects. Patients with frontal lesions showed increased pain thresholds when the stimuli were administered contralateral to the lesion. While the peak-to-peak amplitudes of the N150/P250 components of the somatosensory potentials increased linearly with stimulus intensity in the control subjects, the responses in the frontal group did not change significantly between stimulation at pain and tolerance threshold. There was no evidence for altered pain processing in patients with parietal lobe lesions. The findings of the present study support the hypothesis of an involvement of the frontal cortex in pain perception in humans. Keywords: Pain processing; Somatosensory potentials; Frontal lobe lesions
Empirical evidence for an important role of both the parietal and the frontal cortex in pain perception has emerged from several lines of research. In early case studies, patients with acquired cerebral damage were described who displayed a syndrome termed 'asymbolia for pain' which was characterized by an absence of behavioral reactions to painful stimuli in the presence of intact elementary somatosensory perception. Surgical and postmortem evidence related asymbolia for pain to damage of the posterior parietal areas and of the frontal lobes [12,17, 20]. Electrophysiological recordings in animals yielded nociresponsive neurons in the parietal somatosensory cortex [14] and in cingulate or frontal cortices [2, 18], and single cell recordings in monkeys specifically related the prefrontal cortex to the discrimination of noxious and innocuous stimuli [ 15]. The hypothesis of an involvement of the frontal cortex in pain processing was further supported by lesion and stimulation studies in animals (for a summary see Ref. [11]).
* Corresponding author, Tel.: +49 7071 293244; Fax: +49 7071 295956; E-mail: [email protected].
Investigations with human subjects have mainly used EEG recordings and neuroimaging techniques to explore the cortical processing of painful stimuli. Pain-related changes in EEG alpha and delta activity were observed at parietal and frontal recording sites during the cold pressor test, which involves immersion of the hand or the forearm into freezing water [1,9]. Significant cerebral blood flow changes were seen in the frontal, temporal and parietal cortex during induction of severe pain by this test [7]. Phasic painful heat stimuli ted to activations of primary and secondary somatosensory regions and of frontocingulate areas; the former was thought to be related to sensory-discriminative pain processing and the latter to emotional aspects of pain perception [ 19]. A frequently used objective measure of pain perception in human subjects is the cerebral potential evoked by pain-inducing stimuli, and high correlations are usually seen between subjective pain intensity ratings and the amplitudes of pain-related evoked potentials [3,5]. The present study aimed to further assess the role of the frontal and the parietal cortex in pain processing in humans by investigating subjective pain ratings and somatosensory potentials evoked by painful stimuli in patients with selective damage to these brain areas.
0304-3940/95/$09.50 © 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0304-3940(95)11916-H
138
1. Daum et al. / Neuroscience Letters 197 (1995) 1 3 ~ 1 4 0
Ten patients with unilateral damage of the prefrontal cortex (FL) and seven patients with parietal cortex lesions (PL) participated in this study. The patients had suffered cortical damage as a consequence of ischemia, surgical resection or closed head injury. The lesion was rightsided in six FL patients and three PL patients. The mean age of the FL group was 42.9 years (SD = 15.2) and the mean age of the PL group was 48.4 years (SD = 9.6). The data of the FL group were compared to those of a group of ten healthy control subjects with a mean age of 44.7 years (SD = 14.2); the control subjects (n = 7) for the PL subjects on average were 49.0 years old (SD = 10.7). At the beginning of the testing session, the thresholds for somatosensory perception, pain and pain tolerance were determined. Brief electrical stimuli were applied to the tip of the middle finger of either hand. The upper layers of the epidermis were abrased and a gold pin was applied to the cavity. Application of current through this electrode leads to an activation of A-delta and C-afferents of the nociceptive system (see Ref. [4]). The three different thresholds (stimulus intensities in ktA) were obtained using the method of limits. Based on these individual thresholds, seven stimulus intensities were determined for each subject which were then used to investigate the somatosensory evoked potentials. The following intensities were chosen: the intensities of the somatosensory perception, pain and tolerance threshold, the mean intensity between the perceptual and the pain threshold as well as three intensities which were equidistantly distributed between the pain and the tolerance threshold. In addition, a stimulus intensity of 250ktA was used for all subjects (constant stimulus intensity). Each of these eight stimulus intensities was administered 30 times, resulting in an overall number of 240 stimuli, which were presented in quasi-random order with a mean interstimulus interval of 7.5 s. Each stimulus consisted of a train of five bipolar square pulses and lasted 10 ms. Every stimulus was rated for subjective intensity and aversiveness on a 12 point scale immediately after presentation. The EEG was recorded from 37 electrode positions against linked mastoids (in this paper, only the data for the Cz electrode position are reported). Horizontal and vertical EOGs were registered to correct for ocular artefacts. After measurements were completed, the assessment of thresholds and somatosensory evoked potentials was repeated with stimulus administration to the other hand. For each subject, the sequence of testing was determined randomly. The thresholds for somatosensory perception, pain and tolerance (averaged across both hands) did not differ between the F L patients and the respective control group (all P > 0.46). The PL patients showed marginally higher perceptual thresholds than their controls ( U = 10.5, P = 0.073), whereas there was no significant group difference for the pain and tolerance thresholds. As there was considerable between-subject variability in each group, further analyses were performed to assess differences in
thresholds ipsi- and contralateral to the cortical lesions. For control subjects, 'side of lesion' was randomly allocated to the left or right. For each subject, the following index was calculated: threshold stimulus intensity contralateral divided by the threshold stimulus intensity ipsilateral to the lesion. An index of 1.0 indicates that equal stimulus intensities determined the subjective thresholds at the right and the left hand, whereas values > 1.0 indicate a higher threshold when electrical stimuli were applied contralaterally to the lesion. The indices are illustrated in Fig. 1. These indices were comparable in the PL group and control subjects, whereas the FL group showed marginally or significantly higher indices than the respective control group for the pain (U = 28.0, P = 0.096) and tolerance thresholds (U = 22.0, P = 0.034). This pattern indicates a reduced sensibility to painful stimulation contralateral to the lesion in frontal patients. The EEG registered from Cz was corrected for eye movement artefacts according to the method by Gratton et al. [10] and averaged across the 30 trials of each stimulus intensity. The pain-relevant components of the somatoNO
~
FL
1 50
125
7 O0
075
~3 0.5,9 Percaptior~
i
] NC
Tolerance
Pain
~
PL
1.20
125
1 O0
0.75
0.50
Perception
Pain
Tolerance
Fig. 1. Median scores for the proportion of the contralateral threshold intensity relative to the ipsilateral threshold intensity (FL, frontal lesion patients; PL, parietal lesion patients; NC, control subjects).
L Daum et aL / Neuroscience Letters 197 (1995) 137-140
FL
Intensity
Constant
NC
~..j~*-.-
~
139
PL
Intensity
NC
Constant~
--'I--
20
.
0
.
.
500 ms
.
0
500 ms
--
i
500 ms
0
500 ms
Fig. 2. Somatosensory evoked potentials to brief electrical stimuli of increasing intensity (1, perceptual threshold; 3, pain threshold; 7, tolerance threshold; FL, frontal lesion patients; PL, parietal lesion patients; NC, control subjects).
sensory evoked potential consist of a negativity with a latency of approximately 150 ms (N150) followed by a positive component at 2 5 0 m s (P250) post-stimulus. Peak-to-peak amplitude differences were determined to evaluate the cortical processing of the stimuli (see Ref. [3]). As there were no significant differences when the data for stimulation ipsi- and contralateral to the lesion were compared, the data were averaged across both stimulation sides. The somatosensory evoked potentials are illustrated in Fig. 2. Repeated measures analysis of variance yielded a significant interaction between the factors Group and Intensity (linear trend, F(1,18)=5.96, P = 0 . 0 2 5 ) for the comparison of the FL group and the respective control group. Fig. 2 indicates that the N150/P250 components increase in amplitude with increasing stimulus intensities in the control group, while a much weaker relationship between stimulus intensity and response amplitude was seen in the FL patients. The change in amplitude between perception and pain thresholds (intensities 1 and 3) was similar in both groups (P = 0.37). The mean amplitude differences between potentials evoked by stimulation at
pain and at tolerance threshold (intensities 3 and 7) were 4.6/tV in the control group and 0 . 9 # V in the FL group; this group difference was significant (t(18)=2.38, P = 0.029). In the control group, the evoked response amplitudes were significantly higher at tolerance relative to pain thresholds (t(9) = 3.23, P = 0.010), but the amplitudes did not differ significantly in the FL group (P = 0.19). With the exception of a significant Intensity effect, no statistically significant effects emerged in the comparison of the PL and the respective control subjects. Analysis of the somatosensory potentials evoked by the constant stimulus and of the subjective ratings did not yield any significant group differences between the patient and their respective control groups. Taken together, the present findings indicate that frontal lobe damage alters the cortical processing of painful stimuli, while parietal lobe lesions did not significantly affect pain perception. The latter finding might be due to very small parietal lesions in some of the patients which did not involve the somatosensory areas to a significant degree, as evident by neuroradiological data. The patients with frontal lobe damage, on the other hand,
140
L Daum et al. / Neuroscience Letters 197 (1995) 137-140
s h o w e d r e d u c e d pain sensitivity w h e n stimulated contralaterally to the side o f lesion and no significant change in electrocortical r e s p o n s e amplitudes w h e n stimulus intensity increased f r o m the pain to the tolerance threshold. It should be noted that the intensity effects were intact if non-painful stimuli or stimuli at pain threshold were administered, and the lack of intensity/amplitude relationships only applied to stimuli a b o v e pain threshold. This pattern w o u l d be consistent with the hypothesis that frontal lobe lesions spare e l e m e n t a r y s o m a t o s e n s o r y perception, but affect the p r o c e s s i n g of painful stimuli. In a recent study o f the brain areas i n v o l v e d in the p r o c e s s i n g o f i n n o c u o u s and painful stimuli by means of the d i p o l e s o u r c e localization technique, D o w m a n and D a r c e y [8] interpreted their findings in terms o f hipp o c a m p a l and c i n g u l a t e sources for the N I 5 0 , while no c o n v i n c i n g source c o u l d be localized for the later positivity o c c u r r i n g around 250 ms post-stimulus. Analysis o f m a g n e t i c field potentials [13], h o w e v e r , indicated that the source o f the N 1 5 0 / P 2 5 0 c o m p o n e n t s o f pain-related potentials resided in the prefrontal cortex. This localization is in a c c o r d a n c e with the findings o f the present study. D e s p i t e the lack o f stimulus intensity effects on the N 1 5 0 / P 2 5 0 c o m p o n e n t s o f the pain-related e v o k e d responses, the s u b j e c t i v e pain ratings increased linearly with stimulus intensity in the group o f frontal patients. D i s s o c i a t i o n s o f subjective and o b j e c t i v e measures of pain h a v e been o b s e r v e d in studies on hypnosis, and it has been tentatively s u g g e s t e d that the N 1 5 0 / P 2 5 0 c o m p o nents reflect sensory rather than e v a l u a t i v e aspects of pain p e r c e p t i o n [16]. T h e present data w o u l d thus indicate that frontal l o b e lesions lead to an i m p a i r m e n t in sensoryd i s c r i m i n a t i v e p r o c e s s i n g of painful stimuli. A possible i n v o l v e m e n t o f frontal lobe areas in e v a l u a t i v e pain processing, on the other hand, is implied by the reduced sensibility to painful stimuli contralateral to the lesion. In s u m m a r y , the present results suggest that frontal areas are i n v o l v e d in both aspects of pain processing, and there is increasing e v i d e n c e that the prefrontal cortex forms part o f a n e t w o r k i n v o l v i n g cortical and subcortical structures which t o g e t h e r m e d i a t e the multiple d i m e n s i o n s of pain p e r c e p t i o n [6,111. This research was supported by the D e u t s c h e Fors c h u n g s g e m e i n s c h a f t (Grant Bi 195/24-1). [1] Backonja, M., Howland, E.W., Wang, J., Smith, J., Salinsky, M. and Cleeland, C.S., Tonic changes in alpha power during immersion of the hand in cold water, Electroencephalogr. Clin. Neurophysiol., 79 (1991) 192-203.
[2] Backonja, M. and Miletic, V., Responses of neurons in the rat ventrolateral orbital cortex to phasic and tonic nociceptive stimulation, Brain Res., 557 (1991) 353-355. [3] Bromm, B., Laboratory animal and human volunteers in the assessment of analgesic efficacy. In R.C. Chapman and H. Loeser (Eds.), Issues in Pain Measurement, Raven Press, New York, 1989, pp. 117-144. [4] Bromm, B. and Meier, W., The intracutaneous stimulus: a new pain model for algesimetric studies, Methods Find. Exp. Clin. Pharmacol., 6 (1984) 405-410. [5] Chudler, E.H. and Dong, W.K., The assessment of pain by cerebral evoked potentials, Pain, 16 (1983) 221-244. [6] Coghill, R.C., Talbot, J.D., Evans, A.C., Meyer, E., Gjedde, A., Bushnell, M.C. and Duncan, G.H., Distributed processing of pain and vibration by the human brain, J. Neurosci., 14 (1994) 40954108. [7] Di Piero, V., Ferracuti, S., Sabatini, U., Pantano, P., Cruccu, G. and Lenzi, G.L., A cerebral blood flow study on tonic pain activation in man, Pain, 56 (1994) 167 173. [8] Dowman, R. and Darcey, T.M., SEP topographies elicited by innocuous and noxious sural nerve stimulation. IlI. Dipole source localization analysis, Electrocncephalogr. Clin. Neurophysiol., 92 (1994) 373 391. [9] Ferracuti, S., Seri, S., Mania, D. and Cruccu, G., Quantitative EEG modifications during the Cold Water Pressor Test: hemispheric and hand differences, Int. J. Psychophysiol., 17 (1994) 261-268. [10] Gratton, G., Coles, M.G.H. and Donchin, E., A new method for off-line removal of ocular artifact, Electroencephalogr. Clin. Neurophysiol., 55 (1983) 468-484. [1 I] Hardy, S.G.P. and Haigler, H.J., Prefrontal influences upon the midbrain: a possible route for pain modulation, Brain Res., 339 (1985) 285-293. [12] Hecaen, H. and de Ajuriaguerra, J., Asymbolie de la douleur, etude anatomoelinique, Rev. Neurol., 83 (1950) 300-302. [13] Joseph, J., Howland, E.W., Wakai, R., Backonja, M., Baffa, O., Potenti, F.M. and Clceland, C.S., Late pain-related magnetic field and electric potentials evoked by intracutaneous electric finger stimulation, Electroencephalogr. Clin. Neurophysiol., 80 (1991) 46-52. [14] Kcnshalo, D.R. and Willis, W.I)., The role of the cerebral cortex in pain sensation. In A. Petersen and E.G. Jones (Eds.), The Cerebra[ Cortex, Vol. 9, Plenum Press, New York, 1991, pp. 153-212. [15] Liu, J.L., Han, X.W. and Su, S.N., The role of frontal neurons in pain and acupuncture analgesia, Sci. China. B., 33 (1990) 938945. [16] Meier, W., Klueken, M., Soyka, D. and Bromm, B., Hypnotic hypo- and hyperalgesia: divergent effects on pain ratings and pain-related cerebral potentials, Pain, 53 (1993) 175-18 I. [17] Schilder, P. and Stengel, E., Schmerzasymbolie (Pain asymbolia). Z. Neurol. Psychiatr., 132 ( 1931 ) 367-370. [18] Sikes, R.W. and Vogt. B.A., Nociceptive neurons in area 24 of rabbit cingulate cortex. J. Neurophysiol., 68 (1992) 1720-1732. [19] Talbot, J.D., M,'u'rett, S., Evans, A.C., Meyer, E., Bushnell, M.C. and Duncan, G.H., Multiple representations of pain in human cerebral cortex, Science, 251 ( 1991 ) 1355-1358. [201 Valenslein, E., The Psychosurgery Debate, Freeman, San Francisco, CA. 1980.
Neuroscience Letters 197 (1995) 137-140
NEUROSCIENCE LETT[IS
Pain-related cerebral potentials in patients with frontal or parietal lobe lesions Irene Daum",*, Christoph Braun", Gerlinde Riesch a, Wolfgang Miltner b, Hermann Ackermann c, Markus M. Schugens,, Niels Birbaumer a alnstitute of Medical Psychology and Behavioral Neurobiology, University of Ti~'bingen, Gartenstrasse 29, 72074 Tiibingen, Germany blnstitute of Psychology, University of Jena, Jena, Germany CDepartment of Neurology, University of Tiibingen, Tiibingen, Germany
Received 30 June 1995; revised version received 7 August 1995; accepted 7 August 1995
Abstract The present study investigated the processing of painful electrical stimuli in patients with unilateral frontal or parietal lobe damage and matched control subjects. Patients with frontal lesions showed increased pain thresholds when the stimuli were administered contralateral to the lesion. While the peak-to-peak amplitudes of the N150/P250 components of the somatosensory potentials increased linearly with stimulus intensity in the control subjects, the responses in the frontal group did not change significantly between stimulation at pain and tolerance threshold. There was no evidence for altered pain processing in patients with parietal lobe lesions. The findings of the present study support the hypothesis of an involvement of the frontal cortex in pain perception in humans. Keywords: Pain processing; Somatosensory potentials; Frontal lobe lesions
Empirical evidence for an important role of both the parietal and the frontal cortex in pain perception has emerged from several lines of research. In early case studies, patients with acquired cerebral damage were described who displayed a syndrome termed 'asymbolia for pain' which was characterized by an absence of behavioral reactions to painful stimuli in the presence of intact elementary somatosensory perception. Surgical and postmortem evidence related asymbolia for pain to damage of the posterior parietal areas and of the frontal lobes [12,17, 20]. Electrophysiological recordings in animals yielded nociresponsive neurons in the parietal somatosensory cortex [14] and in cingulate or frontal cortices [2, 18], and single cell recordings in monkeys specifically related the prefrontal cortex to the discrimination of noxious and innocuous stimuli [ 15]. The hypothesis of an involvement of the frontal cortex in pain processing was further supported by lesion and stimulation studies in animals (for a summary see Ref. [11]).
* Corresponding author, Tel.: +49 7071 293244; Fax: +49 7071 295956; E-mail: [email protected].
Investigations with human subjects have mainly used EEG recordings and neuroimaging techniques to explore the cortical processing of painful stimuli. Pain-related changes in EEG alpha and delta activity were observed at parietal and frontal recording sites during the cold pressor test, which involves immersion of the hand or the forearm into freezing water [1,9]. Significant cerebral blood flow changes were seen in the frontal, temporal and parietal cortex during induction of severe pain by this test [7]. Phasic painful heat stimuli ted to activations of primary and secondary somatosensory regions and of frontocingulate areas; the former was thought to be related to sensory-discriminative pain processing and the latter to emotional aspects of pain perception [ 19]. A frequently used objective measure of pain perception in human subjects is the cerebral potential evoked by pain-inducing stimuli, and high correlations are usually seen between subjective pain intensity ratings and the amplitudes of pain-related evoked potentials [3,5]. The present study aimed to further assess the role of the frontal and the parietal cortex in pain processing in humans by investigating subjective pain ratings and somatosensory potentials evoked by painful stimuli in patients with selective damage to these brain areas.
0304-3940/95/$09.50 © 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0304-3940(95)11916-H
138
1. Daum et al. / Neuroscience Letters 197 (1995) 1 3 ~ 1 4 0
Ten patients with unilateral damage of the prefrontal cortex (FL) and seven patients with parietal cortex lesions (PL) participated in this study. The patients had suffered cortical damage as a consequence of ischemia, surgical resection or closed head injury. The lesion was rightsided in six FL patients and three PL patients. The mean age of the FL group was 42.9 years (SD = 15.2) and the mean age of the PL group was 48.4 years (SD = 9.6). The data of the FL group were compared to those of a group of ten healthy control subjects with a mean age of 44.7 years (SD = 14.2); the control subjects (n = 7) for the PL subjects on average were 49.0 years old (SD = 10.7). At the beginning of the testing session, the thresholds for somatosensory perception, pain and pain tolerance were determined. Brief electrical stimuli were applied to the tip of the middle finger of either hand. The upper layers of the epidermis were abrased and a gold pin was applied to the cavity. Application of current through this electrode leads to an activation of A-delta and C-afferents of the nociceptive system (see Ref. [4]). The three different thresholds (stimulus intensities in ktA) were obtained using the method of limits. Based on these individual thresholds, seven stimulus intensities were determined for each subject which were then used to investigate the somatosensory evoked potentials. The following intensities were chosen: the intensities of the somatosensory perception, pain and tolerance threshold, the mean intensity between the perceptual and the pain threshold as well as three intensities which were equidistantly distributed between the pain and the tolerance threshold. In addition, a stimulus intensity of 250ktA was used for all subjects (constant stimulus intensity). Each of these eight stimulus intensities was administered 30 times, resulting in an overall number of 240 stimuli, which were presented in quasi-random order with a mean interstimulus interval of 7.5 s. Each stimulus consisted of a train of five bipolar square pulses and lasted 10 ms. Every stimulus was rated for subjective intensity and aversiveness on a 12 point scale immediately after presentation. The EEG was recorded from 37 electrode positions against linked mastoids (in this paper, only the data for the Cz electrode position are reported). Horizontal and vertical EOGs were registered to correct for ocular artefacts. After measurements were completed, the assessment of thresholds and somatosensory evoked potentials was repeated with stimulus administration to the other hand. For each subject, the sequence of testing was determined randomly. The thresholds for somatosensory perception, pain and tolerance (averaged across both hands) did not differ between the F L patients and the respective control group (all P > 0.46). The PL patients showed marginally higher perceptual thresholds than their controls ( U = 10.5, P = 0.073), whereas there was no significant group difference for the pain and tolerance thresholds. As there was considerable between-subject variability in each group, further analyses were performed to assess differences in
thresholds ipsi- and contralateral to the cortical lesions. For control subjects, 'side of lesion' was randomly allocated to the left or right. For each subject, the following index was calculated: threshold stimulus intensity contralateral divided by the threshold stimulus intensity ipsilateral to the lesion. An index of 1.0 indicates that equal stimulus intensities determined the subjective thresholds at the right and the left hand, whereas values > 1.0 indicate a higher threshold when electrical stimuli were applied contralaterally to the lesion. The indices are illustrated in Fig. 1. These indices were comparable in the PL group and control subjects, whereas the FL group showed marginally or significantly higher indices than the respective control group for the pain (U = 28.0, P = 0.096) and tolerance thresholds (U = 22.0, P = 0.034). This pattern indicates a reduced sensibility to painful stimulation contralateral to the lesion in frontal patients. The EEG registered from Cz was corrected for eye movement artefacts according to the method by Gratton et al. [10] and averaged across the 30 trials of each stimulus intensity. The pain-relevant components of the somatoNO
~
FL
1 50
125
7 O0
075
~3 0.5,9 Percaptior~
i
] NC
Tolerance
Pain
~
PL
1.20
125
1 O0
0.75
0.50
Perception
Pain
Tolerance
Fig. 1. Median scores for the proportion of the contralateral threshold intensity relative to the ipsilateral threshold intensity (FL, frontal lesion patients; PL, parietal lesion patients; NC, control subjects).
L Daum et aL / Neuroscience Letters 197 (1995) 137-140
FL
Intensity
Constant
NC
~..j~*-.-
~
139
PL
Intensity
NC
Constant~
--'I--
20
.
0
.
.
500 ms
.
0
500 ms
--
i
500 ms
0
500 ms
Fig. 2. Somatosensory evoked potentials to brief electrical stimuli of increasing intensity (1, perceptual threshold; 3, pain threshold; 7, tolerance threshold; FL, frontal lesion patients; PL, parietal lesion patients; NC, control subjects).
sensory evoked potential consist of a negativity with a latency of approximately 150 ms (N150) followed by a positive component at 2 5 0 m s (P250) post-stimulus. Peak-to-peak amplitude differences were determined to evaluate the cortical processing of the stimuli (see Ref. [3]). As there were no significant differences when the data for stimulation ipsi- and contralateral to the lesion were compared, the data were averaged across both stimulation sides. The somatosensory evoked potentials are illustrated in Fig. 2. Repeated measures analysis of variance yielded a significant interaction between the factors Group and Intensity (linear trend, F(1,18)=5.96, P = 0 . 0 2 5 ) for the comparison of the FL group and the respective control group. Fig. 2 indicates that the N150/P250 components increase in amplitude with increasing stimulus intensities in the control group, while a much weaker relationship between stimulus intensity and response amplitude was seen in the FL patients. The change in amplitude between perception and pain thresholds (intensities 1 and 3) was similar in both groups (P = 0.37). The mean amplitude differences between potentials evoked by stimulation at
pain and at tolerance threshold (intensities 3 and 7) were 4.6/tV in the control group and 0 . 9 # V in the FL group; this group difference was significant (t(18)=2.38, P = 0.029). In the control group, the evoked response amplitudes were significantly higher at tolerance relative to pain thresholds (t(9) = 3.23, P = 0.010), but the amplitudes did not differ significantly in the FL group (P = 0.19). With the exception of a significant Intensity effect, no statistically significant effects emerged in the comparison of the PL and the respective control subjects. Analysis of the somatosensory potentials evoked by the constant stimulus and of the subjective ratings did not yield any significant group differences between the patient and their respective control groups. Taken together, the present findings indicate that frontal lobe damage alters the cortical processing of painful stimuli, while parietal lobe lesions did not significantly affect pain perception. The latter finding might be due to very small parietal lesions in some of the patients which did not involve the somatosensory areas to a significant degree, as evident by neuroradiological data. The patients with frontal lobe damage, on the other hand,
140
L Daum et al. / Neuroscience Letters 197 (1995) 137-140
s h o w e d r e d u c e d pain sensitivity w h e n stimulated contralaterally to the side o f lesion and no significant change in electrocortical r e s p o n s e amplitudes w h e n stimulus intensity increased f r o m the pain to the tolerance threshold. It should be noted that the intensity effects were intact if non-painful stimuli or stimuli at pain threshold were administered, and the lack of intensity/amplitude relationships only applied to stimuli a b o v e pain threshold. This pattern w o u l d be consistent with the hypothesis that frontal lobe lesions spare e l e m e n t a r y s o m a t o s e n s o r y perception, but affect the p r o c e s s i n g of painful stimuli. In a recent study o f the brain areas i n v o l v e d in the p r o c e s s i n g o f i n n o c u o u s and painful stimuli by means of the d i p o l e s o u r c e localization technique, D o w m a n and D a r c e y [8] interpreted their findings in terms o f hipp o c a m p a l and c i n g u l a t e sources for the N I 5 0 , while no c o n v i n c i n g source c o u l d be localized for the later positivity o c c u r r i n g around 250 ms post-stimulus. Analysis o f m a g n e t i c field potentials [13], h o w e v e r , indicated that the source o f the N 1 5 0 / P 2 5 0 c o m p o n e n t s o f pain-related potentials resided in the prefrontal cortex. This localization is in a c c o r d a n c e with the findings o f the present study. D e s p i t e the lack o f stimulus intensity effects on the N 1 5 0 / P 2 5 0 c o m p o n e n t s o f the pain-related e v o k e d responses, the s u b j e c t i v e pain ratings increased linearly with stimulus intensity in the group o f frontal patients. D i s s o c i a t i o n s o f subjective and o b j e c t i v e measures of pain h a v e been o b s e r v e d in studies on hypnosis, and it has been tentatively s u g g e s t e d that the N 1 5 0 / P 2 5 0 c o m p o nents reflect sensory rather than e v a l u a t i v e aspects of pain p e r c e p t i o n [16]. T h e present data w o u l d thus indicate that frontal l o b e lesions lead to an i m p a i r m e n t in sensoryd i s c r i m i n a t i v e p r o c e s s i n g of painful stimuli. A possible i n v o l v e m e n t o f frontal lobe areas in e v a l u a t i v e pain processing, on the other hand, is implied by the reduced sensibility to painful stimuli contralateral to the lesion. In s u m m a r y , the present results suggest that frontal areas are i n v o l v e d in both aspects of pain processing, and there is increasing e v i d e n c e that the prefrontal cortex forms part o f a n e t w o r k i n v o l v i n g cortical and subcortical structures which t o g e t h e r m e d i a t e the multiple d i m e n s i o n s of pain p e r c e p t i o n [6,111. This research was supported by the D e u t s c h e Fors c h u n g s g e m e i n s c h a f t (Grant Bi 195/24-1). [1] Backonja, M., Howland, E.W., Wang, J., Smith, J., Salinsky, M. and Cleeland, C.S., Tonic changes in alpha power during immersion of the hand in cold water, Electroencephalogr. Clin. Neurophysiol., 79 (1991) 192-203.
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