International Journal o f Psychophysiology, 13 (1992) 137-146 © 1992 Elsevier Science Publishers B.V. All rights reserved 0167-8760/92/$05.00
137
INTPSY 00407
Anxiety, emotion and cerebral blood flow Janick Naveteur a, Jean Claude Roy a, Eric Ovelac b and Marc Steinling b a Laboratoire de Neurosciences du Comportement, B~t SN4, Unit'ersit~ des Sciences et Technologies de Lille, 141leneuced'Ascq (France) and b Sercice Central de M#decine Nucldaire du Pr. Vergnes, H~pital B, CHR de Lille, Lille (France) (Accepted 18 June 1992)
Key words: Regional cerebral blood flow; Anxiety; Emotion; Hemispherical specialization
Regional cerebral blood flow was measured by the xenon inhalation technique using a DSPECT system, during neutral and emotional auditory stimulations. Subjects were 10 high and I0 low trait anxiety, right-handed females. State anxiety was retrospectively assessed. Results indicated a lower rCBF in the high trait or state anxiety subjects who presented also a global rCBF asymmetry in the right > left direction. Additionally, the emotional content of the stimuli interacted significantly with the side of the brain in the thalamic area.
INTRODUCTION The recording of regional cerebral blood flow (rCBF) or regional cerebral glucose metabolic rate (rCMRglu) are important measurements in the experimental study of behavioral or psychological activation. Such measurements provide useful data regarding emotional functioning a n d / or personality traits, especially in the case of anxiety. Differential activation of some areas of the brain, and additionally, bilateral differences have been reported. Table I summarizes the main findings of research dealing with this topic in humans. The diversity of recording techniques, subjects and procedure types is obvious and leads one to consider cautiously any attempt to reach a unitary conclusion. Explanation for the disparity in results may be found in this diversity. For example, the neuroanatomic and neurophysiologic substrates of the various anxiety disorders are almost
Correspondence to: J. Naveteur, Laboratoire de Neurosciences du Comportement, B~t SN4, Universit6 de Lille i, F-59655 Villeneuve d'Ascq Cedex, France.
certainly different. Nevertheless, most results indicated an increase or decrease in rCBF or rCMRglu, and this dichotomy does not easily reflect differences in the type of anxiety. The U-inverted relationship postulated by Gur and Revich's group could account for this fact. Except however in the case of Zohar et al. (1988), inter-studies comparison does not consider that anxiety was higher when decreasing effects were reported than it was for increasing effects as would be expected following this hypothesis. Recent results of Wu et al. (1991) could also suggest that the influence of anxiety could be a complex one which increases the activity of some areas of the brain and decreases others. Literature, however, still seems insufficient to allow for a relevant synthesis of the results regarding differential effects in the brain. Fo go further in the analysis of these experiments, they can be divided into those cgnducted with normal subjects focusing on state anxiety and those conducted with trait anxiety subjects diagnosed as having generalized anxiety disorders, obsessive-compulsive disorders, or panic disorders (see Table I). These subjects were usually compared to normal controls, with or without procedural manipulations of anxiety, or com-
138 TABLE I
Mum results regarding att~iety and regional cerebral blood flow or glucose metabolism Nsub, normal subjects; LA, low anxiety: MA, medium anxiety: HA. high anxiels': GAD. generalized an×leD disorders; OCD. obsessive compulsive disorders; PD, panic disorders; PA, panic attack; S scale, state arz'dety scale; STAi. State and Trait A n x i e ~ Inventory [Spielberger, 1970); lact. inf., lactate infusion; sal. inf., saline infusion.
References
Subjects selection
Effects
Areas of the brain
CBF nitrous oxide technique Kety 1052
one patient
increase during PA
global effect
first exam. > second one
fronto-temporal lobes more marked in the r~ght side mean values (?~
rCBF gamma emission technique with 133Xe Hagstadius and Risberg Nsub 1989 STAI Gur et al. 1987 Nsub S. scale of the STAI Gur et al. 1988 Nsub in gpes LA/MA/HA S. scale of the STAI Mathew et al. 1085 GAD/Nsub Diag.&Slat. Mar, ual of Mental disorders STA! Mathew and Wilson 1988 GAD/Nsub DSMII! and STAi Rodriguez el al. 1989 Nsub STAI Zohar et al. 1988 OCD DSMIII
U inverted relationship with state anxiety curvilinear relat. MA > LA and HA increase as a functmn o[ state anxlet~
extend, cortical areas
increase as a function of state anxiety decrease as a function of state anxiety relaxation > vivo exposure imaginal flt~t~ding > relax.
extend, cortical areas
Dynamic single photon emission computerized axial tomography Stewart el al. 1988 PD/Nsub lact. inf. > sal. inf. or rest DSMill for Nsub or PD without PA lo~ effel for PD vdth PA lact. inf. < sal. inf. or rest for PD with PA rCBF positron emission technique with 150-t12(~ Reiman et al. 1084 PD in absence of P A / Nsub DSMIH &Feighner Test Reiman et al, 1989a PD/Nsub DSMilI-R
Reiman et al. 1989b
Nsub S. scale of the STA! & analog scale
ICMRglu positron emission with 18FFDG Baxter et al. 1087 O C D / N s u b or Unipolar Depressed sub DSMlil, Schedule for Affective Disorders
extend, effect except in occip. & inL temp. areas
no signif, main effect but a right > left asymmetry increase during lactate induc. PA
increase as a function of state anxiety during antidp, of electric, shock
OCD > Nsub or UDsub even with successful drug
front. & temp. areas bilat. right occip. & pariet, areas temp., pariet. & post. cortex temporal lobes whole brain
right occipital a~ea
parahippocampal ~ ' r u s temp. lobes, insular cortex c|austrum or lateral putamen in or near superior coHiculus and left ant. cerebeL vermis bilat, temp. l ~ l e s
left orbital .~:rus trend in the right side of bikl|eral caudate nuclei
139 T A B L E I {confinned)
References
Sub~ects selection
Effects
Giordam e~ al. 1990
Nsub S, scale of the STAI Nsnb S, scale of the STAI OCD/Nsub DSMIH, CompuLsive Acfivi~- CheckI~st simple phobics/Nsub DSM|II PD/Nsub DSMII[
no s~gnif, relationship
G u t el al. 1987 M a r t i r ~ et ak 1 9 q O
Mountz et ak |989 Nordhal e~ a|. I ~
Re|rich ea al, 1983-1984
Nsub STAI
W u el am. 1.91
GAD/Nsub DSMII|
Areas of the brain
neg, correlation for anxiety |evel O C P < Nsub
high
no significant effect phobic stimulus/rest no main effect but during discrimination task, decrease in U inverted relationship with state anxiety G A D > Nsub
G A D < Nsub
pared to themselves, in different experimental contexts. The hypothesis that trait and state anxiety may result in specific effects on neural brain activity has been poorly investigated. The first initial goal of :he present experiment was to more adequately control for these effects. Consequently, on the one hand subjects were selected with high and low trait anxiety and, on the other hand state anxiety, retrospectively assessed, was experimentally modified by the presentation of neutral or aversive stimuli. As~vametricai effects have been underlined in Table I. Although side to side comparisons were not always significant, anxiety appeared to be more often linked to an increase of activity in the right side of the brain. This is in agreement with pharmacological data concerning anxiolitic drugs. In fact, Mathew et al. (1985) showed that a nonsedative dose of diazepam compared to a placebo. induced a more marked right hemispheric reduction of rCBF, especially in ~he frontal lobe. Buschbaum et al. (1987) also observed that benzodiazepines induced a greater right- than left sided metabolic decrease in the occipital cortex. Such findings, obtained with reliable indices of the activity of the brain, sustained the hypothesis
extended conical areas (interp, in t~e U-inv. relat,) whole corte× normalized, prefrontal lateral cortex
left inf, pariet. [obule post. fronto-orbital & mid. frontal areas cerebellum, left inf. area 17 in occip, lobe, right post temp. lobe, prec. front, gyrus sup. temp. lobe, bas. ganglia, white matter temp. pole
of a hemispherical specialization of anxiety (Tucker, 198~,; Gruzelier, 1987; Gruzelier and Phelan, 1991). The asymmetry described could be tentatively integrated into a larger framework of hemispherical specializatio.~ of emotional functions. Thus, the right hemisphere has been described as emotional in contrast to a neutral or cognitive left hemisphere (Schwartz et al., 1975; Bear et Fedio, 1977; Gainotti, 1983). Sackeim et al. (1982) rather considered that the left hemisphere is involved in positive emotions, the right being only involved in negative emotions. All of these hypotheses could serve to integrate the right > left asymmetry suspected in the case of anxiety. To our knowledge, asymmetrical effects of anxiety and emotions have not yet been studied in the same experimental design with measures o ¢ rCBF or rCMRglu. Moreover, the problem of emotional functions per se has not been extensively investigated in this type of research. The second purpose of the present study was to focus on right and left rCBF as a function of anxiety and as a function of experimentally induced emotions. The rCBF induced by negative emotions will be compared to the rCBF recorded during neutral stimulations. A right > !eft asym-
140
metry is expected for high level of anxiety as well as in cases of negative emotions, the bilateral difference being higher for high anxiety and negative emotions together.
107' amplifier was connected to an "Apple lie' computer. A lab-made program recorded the interbit interval with a resolution of 0.l ms. The EKG signal was also continuously visualized by a 'Philips PM 32333" oscilloscope.
METHOD
Procedure
Subjects Twenty volunteer female students in psychology, sociology, or biology took part in this experiment. All were right-handed as assessed by H&aen's laterality test (1984); no subject reported a history of familial sinistrality. Half the subjects presented a high anxiety score {9 or 10) using Cattell's Self-Analysis Sheet (1957); thc other half was composed of low scorers (0. 1 or 2). None of them was considered as depressed according to the Beck's Depression Scale (1984). Due to the criteria and the type of investigation, the selection involved more than 1600 students.
Apparatus Cerebral blood flow was measured using a fast-rotating d e d i c a t e d g a m m a t o m o c a m e r a (Tomomatic 64, Medimatic Corp, Copenhagen), with the 133 xenon inhalation method described by Kanno and Lassen (1979) and the Celcis's algorithm (Ceicis et al., 198t). The SPECT system was fitted with a high sensitivity collimator (FWHM = 16 mm). A complete study takes 4.5 rain during which 80 to 100 mCi of xenon in a 5 1 mixture of air and oxygen was inhaled in a close circuit. Three transaxial brain slices were obtained simultaneously set 20 mm apart at the cantomeathal ( C M ) + 1 cm, +5 cm and + 9 cm k, vels (see Fig. 1) The arterial cerebral input was estimated from the time that the activity lung curve was obtained by placing a narrowly collimated detector over the apex of the right lung. The algorithm is based on a combination of both sequential tomography and the early picture methods, and the record of the time the activity lung curve allowed to obtain the CBF values. CBF was expressed in ml/min per 100 g. The end tidal PaCO 2 value was recorded by means of a Beckmann-LB2 gas analyser. The EKG, processed through a 'Grass RPS
The three tests that are used for the subjects' selection were administered with others that were required by researchers at the University. of Lille. Subjects were convened in groups in order to fill out these questionnaires. The potential subjects were contacted by phone and received detailed information about the CBF procedure. When they arrived at the hospital, the subjects were preseined with detailed instructions once again and asked to sign a written informed consent. Subjects were aware of the nature of the presented stimuli. In order to prevent the use of coping strategies, they were asked not to adopt a defensive attitude against the evoked emotions; they were told that we were interested in the emotions that they would experience but that we did not look at data as it applied to the individual per se. Heart rate recording electrode were attached to the right wrist and the left ankle. The mouthpiece used for the xenon inhalation and a nose pinch were applied. Subjects were then readied for the experiment, and asked to assume a supine position with their eyes closed. After a 5 rain restperiod, two measurements of cerebral blood flow were successively taken, separated by a second rest-period of about 8 min duration. The C B F measurement was of 4 min 30 s duration. During one of these measurements, subjects listened to tape recorded noises of everyday life (preparation of meal, street noise... ); during the other one, they listened to tape-recorded sequences composed of strange and fearful noises (torture sounds with human cries, plaintive howls of dogs, creaking of door, heart beat, ominous step noises... ). The two recordings had been made in a studio and were of similar average and peak to peak intensity. Stimuli have been matched as well as possible both with as regard to the amount of high and low frequency tones and to the rhythm of the sequences. The order of presentation of the stimuli was counterbalanced for one half of
t41
the subjects of each group. Heart rate and the end tidal PaCO 2 value were recorded during bo,h investigations. At the end of the experimental procedure, subjects were asked to fill out questionnaires about their state anxiety. Specifically, they were asked to rate on a seven-point scale 20 anxie~: laden adjectives, taken from Bonis and Lebeau's Q-sort (1975). The emotional impact of the recorded sequences was also retrospectively assessed by rating it on a nine-point scale ranging from - 4 (very unpleasant emotion) to + 4 (very pleasant emotion). Six paired regions of interest (ROls) were drawn in several anatomic areas according to an MRI Atlas (Cabanis et ai., 1986). They corresponded to the low temporal poles at CM + 1 cm level, to frontal and parietal areas on the cortical ribbon and on the thalamic area at CM + 5 cm, and to the frontal and parietal cortex at the highest level (called high frontal and high parietal). Regional blood flow values were calculated for each of these regions. ROls can be seen on Fig. 1.
and HR End tidal PaCO 2 proved to be significantly lower in high trait-anxiety subjects than those with low trait-anxiety (5.38 versus 6.38; F(1/18) = 8.09, P < 0.05). This effect did not interact with the order of presentation nor with the type of stimuli delivered. To examine further the relationship between PaCO 2 and CBF, product-moment correlation was calculated between these two parameters (mean PaCO2 and mean CBF for each s:,bject calculated on both investigations); this correlation was non significant (r(18)= 0.39, NS). H R proved to be significantly lower in high trait-awdety subjects than in low trait-anxiety ones (81.77 versus 93.7 b/rain; F ( 1 / 1 8 ) = 4.94, P < 0.05). This effect did not interact with other experimental factors. As for PaCO 2, product moment correlation was calculated between mean H R and mean CBF. This correlation was low and non-significant (r(18) = - 0.12). During the emotional stimulation, HR was also significantly higher than during the neutral stimuPaCO 2
RESULTS
Psychological data A two-way analysis of variance (anxiety and order of the stimuli), which took into account the four independant groups of subjects, was performed on the mean scores obtained for each
FC
TH
CM+lcm
type of adjective on the state-anxiety test. The influence of the subjects' anxiety ~,a :c.~t performance always reached significance. Compared to the non-anxious subjects, high trait anxiety subjects described themselves as being more anxious (average score on the descriptors of anxiety: 4.22 in the aa_xious subjects and 2. i in the non-anxious ones; F ( 1 / 1 6 ) = 8.66. P < 0.01) and less relaxed (average score of the antonymous: 2.97 in the anxious subjects and 5.07 in the non-anxious ones: ( F ( I / 1 6 ) = 7.99, P < 0.05). Post hoc questionnaires also showed that high trait-anxiety subjects reported more somatic manifestations than those with low anxiety, mainly before the investigations (5.9 symptoms for the anxious subjects versus 0.9 for the non-anxious subjects; F ( I / i 6 ) = 8.62, P < 0.01). The questionnaire proposed at the end of the experiment confirmed the emotional impact of the aversive auditory stimulation. Analysis of variance showed that subjects described the aversive stimulus as significantly more aversive than the neutral stimulation (respectively rated 2.45 and 0.7, F ( I / 1 6 ) = 25.79, P < 0.01).
CM+5cm
CM+gcm
Fig. I. Diagram indicating the different regions of interest. CM, cantomeathal level; PC, parieta! cortex; HPC, high parietal cortex; FC, frontal cortex; HFC, high frontal cortex; TH, thalamic area; TL, temporal lobes.
142
lation: 89.4 versus 85.9 b/rain ( F ( I / 1 6 ) = 5.91, P < 0.05). The effect of the stimulus was not significant for PaCO:. Its-
Regional cerebral blood flow Data were analysed with a multivariate approach of repeated measures for comparison of more than one degree of freedom, u.~ing a PAC Program (Lecoutre and Poitevineau, 1992). A first analysis was performed with the side of the brain, the stimulus type, and the ROIs as repeated measures. The trait anxiety and the order of presentation of the stimulus were considered as dependant factors. Additionally, a second analysis was done, focusing on state anxiety. Subjects were divided by the median into low and high state anxiety subjects. This was done independantly from their trait anxiety, level. All but two of the high state anxiety subjects were among the high trait anxiety subjects.
Main influence of an.~:iety The first analysis showed a significant effect of trait anxiety on CBF ( F ( I / 1 6 ) = 7.3, P < 0.02). High trait anxiety subjects presented a lower CBF than low anxious ones (68.4 versus 78.8 m l / m i n per I00 g). This effect did not significantly interact with the ROIs. However, when each ROt was considered separately, it appeared that the lower
~. .....
G...~-
6S
t
jl TRNT ~ X E T Y
-
- ~ - A~
8"~TE
Fig. 3. Cerebral blood f l t ~ as a funcI~o~ o f ;he subjects" anxiety and the side o f the brain A - . lc¢~ arcxiety sub, eels: A + . high anxiet~ s,~bjecls: LS. lef~ side: RS. righ~ s~de.
rCBF in the high anxiety subjects reached significance only in the parietal (F(1/16)=5.78, P< 0.05), high parietal ( F ( 1 / | 6 ) = 6 . 1 1 , P
137
INTPSY 00407
Anxiety, emotion and cerebral blood flow Janick Naveteur a, Jean Claude Roy a, Eric Ovelac b and Marc Steinling b a Laboratoire de Neurosciences du Comportement, B~t SN4, Unit'ersit~ des Sciences et Technologies de Lille, 141leneuced'Ascq (France) and b Sercice Central de M#decine Nucldaire du Pr. Vergnes, H~pital B, CHR de Lille, Lille (France) (Accepted 18 June 1992)
Key words: Regional cerebral blood flow; Anxiety; Emotion; Hemispherical specialization
Regional cerebral blood flow was measured by the xenon inhalation technique using a DSPECT system, during neutral and emotional auditory stimulations. Subjects were 10 high and I0 low trait anxiety, right-handed females. State anxiety was retrospectively assessed. Results indicated a lower rCBF in the high trait or state anxiety subjects who presented also a global rCBF asymmetry in the right > left direction. Additionally, the emotional content of the stimuli interacted significantly with the side of the brain in the thalamic area.
INTRODUCTION The recording of regional cerebral blood flow (rCBF) or regional cerebral glucose metabolic rate (rCMRglu) are important measurements in the experimental study of behavioral or psychological activation. Such measurements provide useful data regarding emotional functioning a n d / or personality traits, especially in the case of anxiety. Differential activation of some areas of the brain, and additionally, bilateral differences have been reported. Table I summarizes the main findings of research dealing with this topic in humans. The diversity of recording techniques, subjects and procedure types is obvious and leads one to consider cautiously any attempt to reach a unitary conclusion. Explanation for the disparity in results may be found in this diversity. For example, the neuroanatomic and neurophysiologic substrates of the various anxiety disorders are almost
Correspondence to: J. Naveteur, Laboratoire de Neurosciences du Comportement, B~t SN4, Universit6 de Lille i, F-59655 Villeneuve d'Ascq Cedex, France.
certainly different. Nevertheless, most results indicated an increase or decrease in rCBF or rCMRglu, and this dichotomy does not easily reflect differences in the type of anxiety. The U-inverted relationship postulated by Gur and Revich's group could account for this fact. Except however in the case of Zohar et al. (1988), inter-studies comparison does not consider that anxiety was higher when decreasing effects were reported than it was for increasing effects as would be expected following this hypothesis. Recent results of Wu et al. (1991) could also suggest that the influence of anxiety could be a complex one which increases the activity of some areas of the brain and decreases others. Literature, however, still seems insufficient to allow for a relevant synthesis of the results regarding differential effects in the brain. Fo go further in the analysis of these experiments, they can be divided into those cgnducted with normal subjects focusing on state anxiety and those conducted with trait anxiety subjects diagnosed as having generalized anxiety disorders, obsessive-compulsive disorders, or panic disorders (see Table I). These subjects were usually compared to normal controls, with or without procedural manipulations of anxiety, or com-
138 TABLE I
Mum results regarding att~iety and regional cerebral blood flow or glucose metabolism Nsub, normal subjects; LA, low anxiety: MA, medium anxiety: HA. high anxiels': GAD. generalized an×leD disorders; OCD. obsessive compulsive disorders; PD, panic disorders; PA, panic attack; S scale, state arz'dety scale; STAi. State and Trait A n x i e ~ Inventory [Spielberger, 1970); lact. inf., lactate infusion; sal. inf., saline infusion.
References
Subjects selection
Effects
Areas of the brain
CBF nitrous oxide technique Kety 1052
one patient
increase during PA
global effect
first exam. > second one
fronto-temporal lobes more marked in the r~ght side mean values (?~
rCBF gamma emission technique with 133Xe Hagstadius and Risberg Nsub 1989 STAI Gur et al. 1987 Nsub S. scale of the STAI Gur et al. 1988 Nsub in gpes LA/MA/HA S. scale of the STAI Mathew et al. 1085 GAD/Nsub Diag.&Slat. Mar, ual of Mental disorders STA! Mathew and Wilson 1988 GAD/Nsub DSMII! and STAi Rodriguez el al. 1989 Nsub STAI Zohar et al. 1988 OCD DSMIII
U inverted relationship with state anxiety curvilinear relat. MA > LA and HA increase as a functmn o[ state anxlet~
extend, cortical areas
increase as a function of state anxiety decrease as a function of state anxiety relaxation > vivo exposure imaginal flt~t~ding > relax.
extend, cortical areas
Dynamic single photon emission computerized axial tomography Stewart el al. 1988 PD/Nsub lact. inf. > sal. inf. or rest DSMill for Nsub or PD without PA lo~ effel for PD vdth PA lact. inf. < sal. inf. or rest for PD with PA rCBF positron emission technique with 150-t12(~ Reiman et al. 1084 PD in absence of P A / Nsub DSMIH &Feighner Test Reiman et al, 1989a PD/Nsub DSMilI-R
Reiman et al. 1989b
Nsub S. scale of the STA! & analog scale
ICMRglu positron emission with 18FFDG Baxter et al. 1087 O C D / N s u b or Unipolar Depressed sub DSMlil, Schedule for Affective Disorders
extend, effect except in occip. & inL temp. areas
no signif, main effect but a right > left asymmetry increase during lactate induc. PA
increase as a function of state anxiety during antidp, of electric, shock
OCD > Nsub or UDsub even with successful drug
front. & temp. areas bilat. right occip. & pariet, areas temp., pariet. & post. cortex temporal lobes whole brain
right occipital a~ea
parahippocampal ~ ' r u s temp. lobes, insular cortex c|austrum or lateral putamen in or near superior coHiculus and left ant. cerebeL vermis bilat, temp. l ~ l e s
left orbital .~:rus trend in the right side of bikl|eral caudate nuclei
139 T A B L E I {confinned)
References
Sub~ects selection
Effects
Giordam e~ al. 1990
Nsub S, scale of the STAI Nsnb S, scale of the STAI OCD/Nsub DSMIH, CompuLsive Acfivi~- CheckI~st simple phobics/Nsub DSM|II PD/Nsub DSMII[
no s~gnif, relationship
G u t el al. 1987 M a r t i r ~ et ak 1 9 q O
Mountz et ak |989 Nordhal e~ a|. I ~
Re|rich ea al, 1983-1984
Nsub STAI
W u el am. 1.91
GAD/Nsub DSMII|
Areas of the brain
neg, correlation for anxiety |evel O C P < Nsub
high
no significant effect phobic stimulus/rest no main effect but during discrimination task, decrease in U inverted relationship with state anxiety G A D > Nsub
G A D < Nsub
pared to themselves, in different experimental contexts. The hypothesis that trait and state anxiety may result in specific effects on neural brain activity has been poorly investigated. The first initial goal of :he present experiment was to more adequately control for these effects. Consequently, on the one hand subjects were selected with high and low trait anxiety and, on the other hand state anxiety, retrospectively assessed, was experimentally modified by the presentation of neutral or aversive stimuli. As~vametricai effects have been underlined in Table I. Although side to side comparisons were not always significant, anxiety appeared to be more often linked to an increase of activity in the right side of the brain. This is in agreement with pharmacological data concerning anxiolitic drugs. In fact, Mathew et al. (1985) showed that a nonsedative dose of diazepam compared to a placebo. induced a more marked right hemispheric reduction of rCBF, especially in ~he frontal lobe. Buschbaum et al. (1987) also observed that benzodiazepines induced a greater right- than left sided metabolic decrease in the occipital cortex. Such findings, obtained with reliable indices of the activity of the brain, sustained the hypothesis
extended conical areas (interp, in t~e U-inv. relat,) whole corte× normalized, prefrontal lateral cortex
left inf, pariet. [obule post. fronto-orbital & mid. frontal areas cerebellum, left inf. area 17 in occip, lobe, right post temp. lobe, prec. front, gyrus sup. temp. lobe, bas. ganglia, white matter temp. pole
of a hemispherical specialization of anxiety (Tucker, 198~,; Gruzelier, 1987; Gruzelier and Phelan, 1991). The asymmetry described could be tentatively integrated into a larger framework of hemispherical specializatio.~ of emotional functions. Thus, the right hemisphere has been described as emotional in contrast to a neutral or cognitive left hemisphere (Schwartz et al., 1975; Bear et Fedio, 1977; Gainotti, 1983). Sackeim et al. (1982) rather considered that the left hemisphere is involved in positive emotions, the right being only involved in negative emotions. All of these hypotheses could serve to integrate the right > left asymmetry suspected in the case of anxiety. To our knowledge, asymmetrical effects of anxiety and emotions have not yet been studied in the same experimental design with measures o ¢ rCBF or rCMRglu. Moreover, the problem of emotional functions per se has not been extensively investigated in this type of research. The second purpose of the present study was to focus on right and left rCBF as a function of anxiety and as a function of experimentally induced emotions. The rCBF induced by negative emotions will be compared to the rCBF recorded during neutral stimulations. A right > !eft asym-
140
metry is expected for high level of anxiety as well as in cases of negative emotions, the bilateral difference being higher for high anxiety and negative emotions together.
107' amplifier was connected to an "Apple lie' computer. A lab-made program recorded the interbit interval with a resolution of 0.l ms. The EKG signal was also continuously visualized by a 'Philips PM 32333" oscilloscope.
METHOD
Procedure
Subjects Twenty volunteer female students in psychology, sociology, or biology took part in this experiment. All were right-handed as assessed by H&aen's laterality test (1984); no subject reported a history of familial sinistrality. Half the subjects presented a high anxiety score {9 or 10) using Cattell's Self-Analysis Sheet (1957); thc other half was composed of low scorers (0. 1 or 2). None of them was considered as depressed according to the Beck's Depression Scale (1984). Due to the criteria and the type of investigation, the selection involved more than 1600 students.
Apparatus Cerebral blood flow was measured using a fast-rotating d e d i c a t e d g a m m a t o m o c a m e r a (Tomomatic 64, Medimatic Corp, Copenhagen), with the 133 xenon inhalation method described by Kanno and Lassen (1979) and the Celcis's algorithm (Ceicis et al., 198t). The SPECT system was fitted with a high sensitivity collimator (FWHM = 16 mm). A complete study takes 4.5 rain during which 80 to 100 mCi of xenon in a 5 1 mixture of air and oxygen was inhaled in a close circuit. Three transaxial brain slices were obtained simultaneously set 20 mm apart at the cantomeathal ( C M ) + 1 cm, +5 cm and + 9 cm k, vels (see Fig. 1) The arterial cerebral input was estimated from the time that the activity lung curve was obtained by placing a narrowly collimated detector over the apex of the right lung. The algorithm is based on a combination of both sequential tomography and the early picture methods, and the record of the time the activity lung curve allowed to obtain the CBF values. CBF was expressed in ml/min per 100 g. The end tidal PaCO 2 value was recorded by means of a Beckmann-LB2 gas analyser. The EKG, processed through a 'Grass RPS
The three tests that are used for the subjects' selection were administered with others that were required by researchers at the University. of Lille. Subjects were convened in groups in order to fill out these questionnaires. The potential subjects were contacted by phone and received detailed information about the CBF procedure. When they arrived at the hospital, the subjects were preseined with detailed instructions once again and asked to sign a written informed consent. Subjects were aware of the nature of the presented stimuli. In order to prevent the use of coping strategies, they were asked not to adopt a defensive attitude against the evoked emotions; they were told that we were interested in the emotions that they would experience but that we did not look at data as it applied to the individual per se. Heart rate recording electrode were attached to the right wrist and the left ankle. The mouthpiece used for the xenon inhalation and a nose pinch were applied. Subjects were then readied for the experiment, and asked to assume a supine position with their eyes closed. After a 5 rain restperiod, two measurements of cerebral blood flow were successively taken, separated by a second rest-period of about 8 min duration. The C B F measurement was of 4 min 30 s duration. During one of these measurements, subjects listened to tape recorded noises of everyday life (preparation of meal, street noise... ); during the other one, they listened to tape-recorded sequences composed of strange and fearful noises (torture sounds with human cries, plaintive howls of dogs, creaking of door, heart beat, ominous step noises... ). The two recordings had been made in a studio and were of similar average and peak to peak intensity. Stimuli have been matched as well as possible both with as regard to the amount of high and low frequency tones and to the rhythm of the sequences. The order of presentation of the stimuli was counterbalanced for one half of
t41
the subjects of each group. Heart rate and the end tidal PaCO 2 value were recorded during bo,h investigations. At the end of the experimental procedure, subjects were asked to fill out questionnaires about their state anxiety. Specifically, they were asked to rate on a seven-point scale 20 anxie~: laden adjectives, taken from Bonis and Lebeau's Q-sort (1975). The emotional impact of the recorded sequences was also retrospectively assessed by rating it on a nine-point scale ranging from - 4 (very unpleasant emotion) to + 4 (very pleasant emotion). Six paired regions of interest (ROls) were drawn in several anatomic areas according to an MRI Atlas (Cabanis et ai., 1986). They corresponded to the low temporal poles at CM + 1 cm level, to frontal and parietal areas on the cortical ribbon and on the thalamic area at CM + 5 cm, and to the frontal and parietal cortex at the highest level (called high frontal and high parietal). Regional blood flow values were calculated for each of these regions. ROls can be seen on Fig. 1.
and HR End tidal PaCO 2 proved to be significantly lower in high trait-anxiety subjects than those with low trait-anxiety (5.38 versus 6.38; F(1/18) = 8.09, P < 0.05). This effect did not interact with the order of presentation nor with the type of stimuli delivered. To examine further the relationship between PaCO 2 and CBF, product-moment correlation was calculated between these two parameters (mean PaCO2 and mean CBF for each s:,bject calculated on both investigations); this correlation was non significant (r(18)= 0.39, NS). H R proved to be significantly lower in high trait-awdety subjects than in low trait-anxiety ones (81.77 versus 93.7 b/rain; F ( 1 / 1 8 ) = 4.94, P < 0.05). This effect did not interact with other experimental factors. As for PaCO 2, product moment correlation was calculated between mean H R and mean CBF. This correlation was low and non-significant (r(18) = - 0.12). During the emotional stimulation, HR was also significantly higher than during the neutral stimuPaCO 2
RESULTS
Psychological data A two-way analysis of variance (anxiety and order of the stimuli), which took into account the four independant groups of subjects, was performed on the mean scores obtained for each
FC
TH
CM+lcm
type of adjective on the state-anxiety test. The influence of the subjects' anxiety ~,a :c.~t performance always reached significance. Compared to the non-anxious subjects, high trait anxiety subjects described themselves as being more anxious (average score on the descriptors of anxiety: 4.22 in the aa_xious subjects and 2. i in the non-anxious ones; F ( 1 / 1 6 ) = 8.66. P < 0.01) and less relaxed (average score of the antonymous: 2.97 in the anxious subjects and 5.07 in the non-anxious ones: ( F ( I / 1 6 ) = 7.99, P < 0.05). Post hoc questionnaires also showed that high trait-anxiety subjects reported more somatic manifestations than those with low anxiety, mainly before the investigations (5.9 symptoms for the anxious subjects versus 0.9 for the non-anxious subjects; F ( I / i 6 ) = 8.62, P < 0.01). The questionnaire proposed at the end of the experiment confirmed the emotional impact of the aversive auditory stimulation. Analysis of variance showed that subjects described the aversive stimulus as significantly more aversive than the neutral stimulation (respectively rated 2.45 and 0.7, F ( I / 1 6 ) = 25.79, P < 0.01).
CM+5cm
CM+gcm
Fig. I. Diagram indicating the different regions of interest. CM, cantomeathal level; PC, parieta! cortex; HPC, high parietal cortex; FC, frontal cortex; HFC, high frontal cortex; TH, thalamic area; TL, temporal lobes.
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lation: 89.4 versus 85.9 b/rain ( F ( I / 1 6 ) = 5.91, P < 0.05). The effect of the stimulus was not significant for PaCO:. Its-
Regional cerebral blood flow Data were analysed with a multivariate approach of repeated measures for comparison of more than one degree of freedom, u.~ing a PAC Program (Lecoutre and Poitevineau, 1992). A first analysis was performed with the side of the brain, the stimulus type, and the ROIs as repeated measures. The trait anxiety and the order of presentation of the stimulus were considered as dependant factors. Additionally, a second analysis was done, focusing on state anxiety. Subjects were divided by the median into low and high state anxiety subjects. This was done independantly from their trait anxiety, level. All but two of the high state anxiety subjects were among the high trait anxiety subjects.
Main influence of an.~:iety The first analysis showed a significant effect of trait anxiety on CBF ( F ( I / 1 6 ) = 7.3, P < 0.02). High trait anxiety subjects presented a lower CBF than low anxious ones (68.4 versus 78.8 m l / m i n per I00 g). This effect did not significantly interact with the ROIs. However, when each ROt was considered separately, it appeared that the lower
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Fig. 3. Cerebral blood f l t ~ as a funcI~o~ o f ;he subjects" anxiety and the side o f the brain A - . lc¢~ arcxiety sub, eels: A + . high anxiet~ s,~bjecls: LS. lef~ side: RS. righ~ s~de.
rCBF in the high anxiety subjects reached significance only in the parietal (F(1/16)=5.78, P< 0.05), high parietal ( F ( 1 / | 6 ) = 6 . 1 1 , P
