- Email: [email protected]
Body image distortion reveals amygdala activation in patients with anorexia nervosa – a functional magnetic resonance imaging study
Neuroscience Letters 326 (2002) 25–28 www.elsevier.com/locate/neulet
Body image distortion reveals amygdala activation in patients with anorexia nervosa – a functional magnetic resonance imaging study Gert Seeger a,*, Dieter F. Braus b, Matthias Ruf b, Ursula Goldberger a, Martin H. Schmidt a a
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, P.O. Box 12 21 20, 68072 Mannheim, Germany b NMR-Research in Psychiatry, Central Institute of Mental Health, 68072 Mannheim, Germany Received 31 December 2001; received in revised form 22 March 2002; accepted 22 March 2002
Abstract In anorexia nervosa patients, body image distortion is a core and often persistent symptom, which continues to pose a risk for relapse even after weight recovery. Using functional magnetic resonance imaging (fMRI) in combination with a computer-based life image distortion technique, we stimulated female anorectic patients and healthy controls with digital pictures of their own body image, individually distorted by themselves. In anorectic patients, stimulation with their own body image was associated with activation in the right amygdala, the right gyrus fusiformis and the brainstem region. Our preliminary findings indicate an activation of the brain’s ‘fear network’ and underscore the need for examination of body image distortions in anorectic patients with a fMRI design to further evaluate the course of this disturbance in a longitudinal approach. q 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Functional magnetic resonance imaging; Amygdala; Anxiety; Anorexia nervosa; Body image distortion
Eating disorders (ED) have classically been associated with concerns about body shape and size which manifest themselves mainly as intense fear of weight gain (DSM-IV criteria; Diagnostic and Statistical Manual of the American Psychiatric Association). Anorexia nervosa (AN) patients not only perceive but actually see their body as being fatter than it is, especially in the abdomen, buttocks or thighs. In comparison to women without an ED, they not only display harsher judgment concerning their own body size and shape, but are also much more critical of other women’s figures [20]. Although considerable progress has been achieved in the treatment of body image distortion through mirror confrontation therapy, anorectic individuals, especially during weight gain, often continue to be afraid of being confronted with the shape of their body and avoid any exposure. Over the past few years, the physiological mechanisms of anxiety have been investigated in numerous studies using different methods. These have led to the hypothesis that the brain’s ‘fear network’ is centered in the amygdala [11]. * Corresponding author. Tel.: 149-202-2549-805; fax: 149-2022549-805. E-mail address: [email protected] (G. Seeger).
Several functional magnetic resonance imaging (fMRI) studies show a connection between functional and morphological changes of the amygdala and the influence of fear [1,2,15,17]. In patients with generalized anxiety disorder, both the right and total amygdala volumes were significantly larger. These results are consistent with assumptions that alterations in the structure and function of the amygdala may be associated with anxiety disorders [6]. With regard to AN, several studies using different neuroimaging techniques revealed morphological and functional alterations. Patients with AN show enlarged cerebrospinal fluid spaces and reductions in gray and white matter that are only partially reversible with weight recovery [12]. Positron emission tomography (PET) revealed caudate hyperactivity during the anorectic state, as well as several mild right–left asymmetries possibly related to alterations in patients’ mental state, as for example vigilance or depression [13]. Regional cerebral blood flow (rCBF) radioisotope scans showed a reduced rCBF in childhood-onset AN [9]. Some results also suggest alterations in stimulus processing in AN patients. One study using visually evoked brainphysiological responses showed an increased negative slow wave in anorectic patients after confrontation with the silhouette of an overweight female body (phobic stimulus)
0304-3940/02/$ - see front matter q 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S03 04 - 394 0( 0 2) 00 31 2- 9
26
G. Seeger et al. / Neuroscience Letters 326 (2002) 25–28
[19]. In a fMRI study comparing brain activity of anorectic patients and healthy controls after confrontation with highcompared to low-caloric drinks, anorectic individuals also revealed a specific activation in the left amygdala–hippocampal region, the insula, and the anterior cingulate gyrus [7]. Using PET, a behavioral challenge study on symptom provocation with high-calorie food stimuli demonstrated greater mean rCBF values within the medial temporal lobes as well as exaggerated responses in the visual association cortex similar to phobic fear [10]. As there are no studies using fMRI to investigate the effects of body image distortion on the amygdala, we decided to carry out such a study on the basis of the above mentioned findings using digital body images individually distorted by AN patients and healthy controls for symptom provocation. Three carefully selected female inpatients with AN (mean age, 17.0 ^ 0.5 years) and three healthy controls (mean age, 17.5 ^ 0.5 years) were included in the study. All patients met the DSM-IV criteria for the diagnosis of AN and were examined at the beginning of their inpatient treatment. None of the three patients showed comorbid disturbances fulfilling the DSM-IV criteria for obsessive–compulsive disorder, depression, anxiety or any other disorder. The two groups did not differ with regard to age, intelligence or educational level. All patients and controls were free of medication. For registration and evaluation of subjective anorectic features (disorders of body schemes), self-assessments were carried out using the Body Shape Questionnaire [5], in which anorectic patients clearly differed from our healthy participants with regard to their subjective assessment of body shape. For anorectic patients, the average body mass index was 15.3 ^ 0.6, and 18.7 ^ 0.6 for our healthy controls. Informed consent was obtained from both patients and controls. Before fMRI examination, together with the patients and healthy controls, we had individually developed body images for symptom provocation by means of a computer-based image distortion technique allowing for distortion of either the whole body or individual parts (i.e. increased thigh, breast or tummy circumference). Using these images, the fMRI paradigm for the individual participant of the study was created, consisting of three categories of stimuli: (1), images with subjective maximum unacceptability of participant’s own body (target); 2), images with subjective maximum unacceptability of another woman’s body image (nontarget); and (3), abstract images with a random mix of colors comprised in participants’ own body images (neutral). The fMRI paradigm was composed of ten epochs (each lasting five times 19.8 s, or a total of 99 s), during which target, non-target and neutral images were presented alternating in a block design with the image of a cross for visual fixation as absolute baseline. Each stimulus was presented 19.8 s, the order of the target and non-target condition was counterbalanced within the experiment. One epoch consisted of five presentations starting with a target or
non-target image followed by two periods of fixation. Then a neutral next image was presented followed by one period of fixation. A vacuum pad was used to improve head fixation and to minimize involuntary head movement. Imaging was performed on a standard clinical 1.5 T MRI Scanner (Siemens Vision w). For fMRI, an echo planar imaging-sequence (TE ¼ 60 ms, TR ¼ 0:6 ms, a ¼ 908, repetition time every 3.3 s) with an in-plane resolution of 64 £ 64 pixels (24 slices, 4 mm thickness, 1 mm gap) was used. For anatomical reference, a 3D Magnetization Prepared Rapid Gradient Echo image data set was acquired. fMRI slices were oriented axially to the AC–PC plane. Each functional T2* slice was imaged 305 times with the first five images discarded to eliminate T1 effects. Data analysis was performed using custom software [8]. Special care was taken to exclude head motion artifacts. The functional images and the anatomical reference were spatially coregistered and transformed into a standard space corresponding to the atlas of Talairach and Tournoux [21]. Statistical analysis was performed by modeling three predictors according to the different experimental conditions (box car functions convoluted with a function which accounts for the hemodynamic response) as explanatory variables within the context of the general linear model on a voxel-by-voxel basis. For each subject, time courses were averaged across equal stimulations. Data were analyzed for each subject individually and by combining all subjects of each group (patients and controls) for group analysis. Patients and controls did not differ in overall head motions during the fMRI experiments. Qualitative evaluation of the structural images by a radiologist blind to subject status revealed no structural abnormalities. Comparing target, non-target and neutral pictures versus baseline, the group analysis of anorectic patients and healthy subjects revealed—as expected—significant (P , 0:05) BOLD-activation in the lateral geniculate nuclei, the primary visual cortex (V1) and extrastriate areas (V2–V5) with a predominance in the ventral visual stream. The comparison of the averaged time course of the signal change due to the target pictures (own body image distortion) versus an average of non-target and neutral pictures did, however, only show anorectic patients to have a significant (F ¼ 13:58, P , 0:001, uncorrected) activation in the brainstem (x ¼ 4, y ¼ 225, z ¼ 215), the right amygdala (x ¼ 28, y ¼ 22, z ¼ 215), as well as the right gyrus fusiformis (x ¼ 39, y ¼ 238, z ¼ 215), a clear sign for a specific effect of the target pictures on brain function (Fig. 1). Our data are the first to show right amygdala activation in AN patients when they are confronted with their own distorted body shape. Patients with anxiety disorders also show amygdala activation which is interpreted as being caused by aversive or threat-related events and by a potential recall of aversive memories [3]. Amygdala signal change in response to pictures with negative versus neutral valence is reported in another fMRI study [14]. A similar activation was
G. Seeger et al. / Neuroscience Letters 326 (2002) 25–28
27
Fig. 1. Presentation of target stimuli (patients body images) elicits an activation of: (1), right amygdala; (2), brainstem; and (3), right gyrus fusiformis in anorectic patients only (right) but not control subjects (left). The small diagrams show the averaged time course of the BOLD response (mean signal change in % ^ SD) for each condition in the three brain areas with the blue line representing the response to target, dark green the non-target condition and light green the abstract neutral pictures.
seen in patients with posttraumatic stress disorder during PET scanning of provoked stimuli [18]. In a PET study with normal subjects, Cahill et al. reported an increased glucose metabolism in the right amygdala correlated with increased recall of emotionally arousing events [4]. As we could exclude comorbid disorders in our patients, our results support the hypothesis of an activation of the right amygdala through an aversive, anxiety-related stimulus. Overall, our findings are consistent with the large body of data from non-human studies suggesting the amygdala as a key structure for extracting the affective significance from external stimuli [14]. Our findings must clearly be regarded as preliminary due to the small number of anorectic patients available for this study, but they support Lang’s suggestion to examine anorectic patients with a fMRI design to further elucidate disturbances in the affective network in a longitudinal approach [16]. Future studies should also include the phase of weight gain and take into consideration therapeutic measures such as behavioral (mirror confrontation) and/or pharmacological therapy. The authors would like to thank Elena Thiel and Daniela Stramke for their excellent cooperation.
[1] Birbaumer, N., Grodd, W., Diedrich, O., Klose, U., Erb, M., Lotze, M., Schneider, F., Weiss, U. and Flor, H., fMRI reveals
[2]
[3]
[4]
[5]
[6]
[7]
[8]
amygdala activation to human faces in social phobics, NeuroReport, 9 (1998) 1223–1226. Breiter, H.C., Etcoff, N.L., Whalen, P.J., Kennedy, W.A., Rauch, S.L., Buckner, R.L., Strauss, M.M., Hyman, S.E. and Rosen, B.R., Response and habituation of the human amygdala during visual processing of facial expression, Neuron, 17 (1996) 875–887. Breiter, H.C., Rauch, S.L., Kwong, K.K., Baker, J.R., Weisskoff, R.M., Kennedy, D.N., Kendrick, A.D., Davis, T.L., Jiang, A., Cohen, M.S., Stern, C.E., Belliveau, J.W., Baer, L., O’Sullivan, R.L., Savage, C.R., Jenike, M.A. and Rosen, B.R., Functional magnetic resonance imaging of symptom provocation in obsessive–compulsive disorder, Arch. Gen. Psychiatry, 53 (1996) 595–606. Cahill, L., Haier, R.J., Fallon, J., Alkire, M.T., Tang, C., Keator, D., Wu, J. and McGaugh, J.L., Amygdala activity at encoding correlated with long-term, free recall of emotional information, Proc. Natl. Acad. Sci. USA, 93 (1996) 8016–8021. Cooper, P.J., Taylor, M.J., Cooper, Z. and Fairburn, C.G., The development and validation of the body shape questionnaire, Int. J. Eating Disord., 6 (1987) 485–494. De Bellis, M.D., Casey, B.J., Dahl, R.E., Birmaher, B., Williamson, D.E., Thomas, K.M., Axelson, D.A., Frustaci, K., Boring, A.M., Hall, J. and Ryan, N.D., A pilot study of amygdala volumes in pediatric generalized anxiety disorder, Biol. Psychiatry, 48 (2000) 51–57. Ellison, Z., Foong, J., Howard, R., Bullmore, E., Williams, S. and Treasure, J., Functional anatomy of calorie fear in anorexia nervosa (Letter), Lancet, 352 (1998) 1192. Goebel, R., Khorram-Sefat, D., Muckli, L., Hacker, H. and Singer, W., The constructive nature of vision: direct
28
[9]
[10]
[11]
[12]
[13] [14]
[15]
G. Seeger et al. / Neuroscience Letters 326 (2002) 25–28 evidence from functional magnetic resonance imaging studies of apparent motion and motion imagery, Eur. J. Neurosci., 10 (1998) 1563–1573. Gordon, I., Lask, B., Bryant-Waugh, R., Christie, D. and Timimi, S., Childhood-onset anorexia nervosa: towards identifying a biological substrate, Int. J. Eating Disord., 22 (1997) 159–165. Gordon, C.M., Dougherty, D.D., Fischman, A.J., Emans, S.J., Grace, E., Lamm, R., Alpert, N.M., Majzoub, J.A. and Rauch, S.L., Neural substrates of anorexia nervosa: a behavioral challenge study with positron emission tomography, J. Pediatr., 139 (2001) 51–57. Gorman, J.M., Kent, J.M., Sullivan, G.M. and Coplan, J.D., Neuroanatomical hypothesis of panic disorder, revised, Am. J. Psychiatry, 157 (2000) 493–505. Hendren, R.L., De Backer, I. and Pandina, G.J., Review of neuroimaging studies of child and adolescent psychiatric disorders from the past 10 years, J. Am. Acad. Child Adolesc. Psychiatry, 39 (2000) 815–828. Herholz, K., Neuroimaging in anorexia nervosa, Psychiatry Res., 62 (1996) 105–110. Irwin, W., Davidson, R.J., Lowe, M.J., Mock, B.J., Sorenson, J.A. and Turski, P.A., Human amygdala activation detected with echo-planar functional magnetic resonance imaging, NeuroReport, 7 (1996) 1765–1769. LaBar, K.S., Gatenby, J.C., Gore, J.C., LeDoux, J.E. and
[16]
[17]
[18]
[19]
[20]
[21]
Phelps, E.A., Human amygdala activation during conditioned fear acquisition and extinction: a mixed-trial fMRI study, Neuron, 20 (1998) 937–945. Lang, P.J., Bradley, M.M., Fitzsimmons, J.R., Cuthbert, B.N., Scott, J.D., Moulder, B. and Nangia, V., Emotional arousal and activation of the visual cortex: an fMRI analysis, Psychophysiology, 35 (1998) 199–210. Phillips, M.L., Young, A.W., Scott, S.K., Calder, A.J., Andrew, C., Giampietro, V., Williams, S.C., Bullmore, E.T., Brammer, M. and Gray, J.A., Neural responses to facial and vocal expressions of fear and disgust, Proc. R. Soc. Lond. B Biol. Sci., 265 (1998) 1809–1817. Rauch, S. and Shin, L., Functional neuroimaging studies in posttraumatic stress disorder, In R. Yehuda and A.C. McFarlane (Eds.) , Psychobiology of posttraumatic stress disorder. New York Academy of Sciences, New York, 1997, pp. 83–98. Seeger, G. and Lehmkuhl, G., Hirnelektrische Korrelate der Verarbeitung Affektiver versus Neutraler Reize bei Jugendlichen mit Anorexia Nervosa, Springer–Verlag, Berlin, 1993, pp. 375–379. Smeets, M.A., Body size categorization in anorexia nervosa using a morphing instrument, Int. J. Eating Disord., 25 (1999) 451–455. Talairach, J. and Tournoux, P., Co-planar Stereotactic Atlas of the Human Brain, Georg Thieme Verlag, Stuttgart, Germany, 1988.
Body image distortion reveals amygdala activation in patients with anorexia nervosa – a functional magnetic resonance imaging study Gert Seeger a,*, Dieter F. Braus b, Matthias Ruf b, Ursula Goldberger a, Martin H. Schmidt a a
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, P.O. Box 12 21 20, 68072 Mannheim, Germany b NMR-Research in Psychiatry, Central Institute of Mental Health, 68072 Mannheim, Germany Received 31 December 2001; received in revised form 22 March 2002; accepted 22 March 2002
Abstract In anorexia nervosa patients, body image distortion is a core and often persistent symptom, which continues to pose a risk for relapse even after weight recovery. Using functional magnetic resonance imaging (fMRI) in combination with a computer-based life image distortion technique, we stimulated female anorectic patients and healthy controls with digital pictures of their own body image, individually distorted by themselves. In anorectic patients, stimulation with their own body image was associated with activation in the right amygdala, the right gyrus fusiformis and the brainstem region. Our preliminary findings indicate an activation of the brain’s ‘fear network’ and underscore the need for examination of body image distortions in anorectic patients with a fMRI design to further evaluate the course of this disturbance in a longitudinal approach. q 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Functional magnetic resonance imaging; Amygdala; Anxiety; Anorexia nervosa; Body image distortion
Eating disorders (ED) have classically been associated with concerns about body shape and size which manifest themselves mainly as intense fear of weight gain (DSM-IV criteria; Diagnostic and Statistical Manual of the American Psychiatric Association). Anorexia nervosa (AN) patients not only perceive but actually see their body as being fatter than it is, especially in the abdomen, buttocks or thighs. In comparison to women without an ED, they not only display harsher judgment concerning their own body size and shape, but are also much more critical of other women’s figures [20]. Although considerable progress has been achieved in the treatment of body image distortion through mirror confrontation therapy, anorectic individuals, especially during weight gain, often continue to be afraid of being confronted with the shape of their body and avoid any exposure. Over the past few years, the physiological mechanisms of anxiety have been investigated in numerous studies using different methods. These have led to the hypothesis that the brain’s ‘fear network’ is centered in the amygdala [11]. * Corresponding author. Tel.: 149-202-2549-805; fax: 149-2022549-805. E-mail address: [email protected] (G. Seeger).
Several functional magnetic resonance imaging (fMRI) studies show a connection between functional and morphological changes of the amygdala and the influence of fear [1,2,15,17]. In patients with generalized anxiety disorder, both the right and total amygdala volumes were significantly larger. These results are consistent with assumptions that alterations in the structure and function of the amygdala may be associated with anxiety disorders [6]. With regard to AN, several studies using different neuroimaging techniques revealed morphological and functional alterations. Patients with AN show enlarged cerebrospinal fluid spaces and reductions in gray and white matter that are only partially reversible with weight recovery [12]. Positron emission tomography (PET) revealed caudate hyperactivity during the anorectic state, as well as several mild right–left asymmetries possibly related to alterations in patients’ mental state, as for example vigilance or depression [13]. Regional cerebral blood flow (rCBF) radioisotope scans showed a reduced rCBF in childhood-onset AN [9]. Some results also suggest alterations in stimulus processing in AN patients. One study using visually evoked brainphysiological responses showed an increased negative slow wave in anorectic patients after confrontation with the silhouette of an overweight female body (phobic stimulus)
0304-3940/02/$ - see front matter q 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S03 04 - 394 0( 0 2) 00 31 2- 9
26
G. Seeger et al. / Neuroscience Letters 326 (2002) 25–28
[19]. In a fMRI study comparing brain activity of anorectic patients and healthy controls after confrontation with highcompared to low-caloric drinks, anorectic individuals also revealed a specific activation in the left amygdala–hippocampal region, the insula, and the anterior cingulate gyrus [7]. Using PET, a behavioral challenge study on symptom provocation with high-calorie food stimuli demonstrated greater mean rCBF values within the medial temporal lobes as well as exaggerated responses in the visual association cortex similar to phobic fear [10]. As there are no studies using fMRI to investigate the effects of body image distortion on the amygdala, we decided to carry out such a study on the basis of the above mentioned findings using digital body images individually distorted by AN patients and healthy controls for symptom provocation. Three carefully selected female inpatients with AN (mean age, 17.0 ^ 0.5 years) and three healthy controls (mean age, 17.5 ^ 0.5 years) were included in the study. All patients met the DSM-IV criteria for the diagnosis of AN and were examined at the beginning of their inpatient treatment. None of the three patients showed comorbid disturbances fulfilling the DSM-IV criteria for obsessive–compulsive disorder, depression, anxiety or any other disorder. The two groups did not differ with regard to age, intelligence or educational level. All patients and controls were free of medication. For registration and evaluation of subjective anorectic features (disorders of body schemes), self-assessments were carried out using the Body Shape Questionnaire [5], in which anorectic patients clearly differed from our healthy participants with regard to their subjective assessment of body shape. For anorectic patients, the average body mass index was 15.3 ^ 0.6, and 18.7 ^ 0.6 for our healthy controls. Informed consent was obtained from both patients and controls. Before fMRI examination, together with the patients and healthy controls, we had individually developed body images for symptom provocation by means of a computer-based image distortion technique allowing for distortion of either the whole body or individual parts (i.e. increased thigh, breast or tummy circumference). Using these images, the fMRI paradigm for the individual participant of the study was created, consisting of three categories of stimuli: (1), images with subjective maximum unacceptability of participant’s own body (target); 2), images with subjective maximum unacceptability of another woman’s body image (nontarget); and (3), abstract images with a random mix of colors comprised in participants’ own body images (neutral). The fMRI paradigm was composed of ten epochs (each lasting five times 19.8 s, or a total of 99 s), during which target, non-target and neutral images were presented alternating in a block design with the image of a cross for visual fixation as absolute baseline. Each stimulus was presented 19.8 s, the order of the target and non-target condition was counterbalanced within the experiment. One epoch consisted of five presentations starting with a target or
non-target image followed by two periods of fixation. Then a neutral next image was presented followed by one period of fixation. A vacuum pad was used to improve head fixation and to minimize involuntary head movement. Imaging was performed on a standard clinical 1.5 T MRI Scanner (Siemens Vision w). For fMRI, an echo planar imaging-sequence (TE ¼ 60 ms, TR ¼ 0:6 ms, a ¼ 908, repetition time every 3.3 s) with an in-plane resolution of 64 £ 64 pixels (24 slices, 4 mm thickness, 1 mm gap) was used. For anatomical reference, a 3D Magnetization Prepared Rapid Gradient Echo image data set was acquired. fMRI slices were oriented axially to the AC–PC plane. Each functional T2* slice was imaged 305 times with the first five images discarded to eliminate T1 effects. Data analysis was performed using custom software [8]. Special care was taken to exclude head motion artifacts. The functional images and the anatomical reference were spatially coregistered and transformed into a standard space corresponding to the atlas of Talairach and Tournoux [21]. Statistical analysis was performed by modeling three predictors according to the different experimental conditions (box car functions convoluted with a function which accounts for the hemodynamic response) as explanatory variables within the context of the general linear model on a voxel-by-voxel basis. For each subject, time courses were averaged across equal stimulations. Data were analyzed for each subject individually and by combining all subjects of each group (patients and controls) for group analysis. Patients and controls did not differ in overall head motions during the fMRI experiments. Qualitative evaluation of the structural images by a radiologist blind to subject status revealed no structural abnormalities. Comparing target, non-target and neutral pictures versus baseline, the group analysis of anorectic patients and healthy subjects revealed—as expected—significant (P , 0:05) BOLD-activation in the lateral geniculate nuclei, the primary visual cortex (V1) and extrastriate areas (V2–V5) with a predominance in the ventral visual stream. The comparison of the averaged time course of the signal change due to the target pictures (own body image distortion) versus an average of non-target and neutral pictures did, however, only show anorectic patients to have a significant (F ¼ 13:58, P , 0:001, uncorrected) activation in the brainstem (x ¼ 4, y ¼ 225, z ¼ 215), the right amygdala (x ¼ 28, y ¼ 22, z ¼ 215), as well as the right gyrus fusiformis (x ¼ 39, y ¼ 238, z ¼ 215), a clear sign for a specific effect of the target pictures on brain function (Fig. 1). Our data are the first to show right amygdala activation in AN patients when they are confronted with their own distorted body shape. Patients with anxiety disorders also show amygdala activation which is interpreted as being caused by aversive or threat-related events and by a potential recall of aversive memories [3]. Amygdala signal change in response to pictures with negative versus neutral valence is reported in another fMRI study [14]. A similar activation was
G. Seeger et al. / Neuroscience Letters 326 (2002) 25–28
27
Fig. 1. Presentation of target stimuli (patients body images) elicits an activation of: (1), right amygdala; (2), brainstem; and (3), right gyrus fusiformis in anorectic patients only (right) but not control subjects (left). The small diagrams show the averaged time course of the BOLD response (mean signal change in % ^ SD) for each condition in the three brain areas with the blue line representing the response to target, dark green the non-target condition and light green the abstract neutral pictures.
seen in patients with posttraumatic stress disorder during PET scanning of provoked stimuli [18]. In a PET study with normal subjects, Cahill et al. reported an increased glucose metabolism in the right amygdala correlated with increased recall of emotionally arousing events [4]. As we could exclude comorbid disorders in our patients, our results support the hypothesis of an activation of the right amygdala through an aversive, anxiety-related stimulus. Overall, our findings are consistent with the large body of data from non-human studies suggesting the amygdala as a key structure for extracting the affective significance from external stimuli [14]. Our findings must clearly be regarded as preliminary due to the small number of anorectic patients available for this study, but they support Lang’s suggestion to examine anorectic patients with a fMRI design to further elucidate disturbances in the affective network in a longitudinal approach [16]. Future studies should also include the phase of weight gain and take into consideration therapeutic measures such as behavioral (mirror confrontation) and/or pharmacological therapy. The authors would like to thank Elena Thiel and Daniela Stramke for their excellent cooperation.
[1] Birbaumer, N., Grodd, W., Diedrich, O., Klose, U., Erb, M., Lotze, M., Schneider, F., Weiss, U. and Flor, H., fMRI reveals
[2]
[3]
[4]
[5]
[6]
[7]
[8]
amygdala activation to human faces in social phobics, NeuroReport, 9 (1998) 1223–1226. Breiter, H.C., Etcoff, N.L., Whalen, P.J., Kennedy, W.A., Rauch, S.L., Buckner, R.L., Strauss, M.M., Hyman, S.E. and Rosen, B.R., Response and habituation of the human amygdala during visual processing of facial expression, Neuron, 17 (1996) 875–887. Breiter, H.C., Rauch, S.L., Kwong, K.K., Baker, J.R., Weisskoff, R.M., Kennedy, D.N., Kendrick, A.D., Davis, T.L., Jiang, A., Cohen, M.S., Stern, C.E., Belliveau, J.W., Baer, L., O’Sullivan, R.L., Savage, C.R., Jenike, M.A. and Rosen, B.R., Functional magnetic resonance imaging of symptom provocation in obsessive–compulsive disorder, Arch. Gen. Psychiatry, 53 (1996) 595–606. Cahill, L., Haier, R.J., Fallon, J., Alkire, M.T., Tang, C., Keator, D., Wu, J. and McGaugh, J.L., Amygdala activity at encoding correlated with long-term, free recall of emotional information, Proc. Natl. Acad. Sci. USA, 93 (1996) 8016–8021. Cooper, P.J., Taylor, M.J., Cooper, Z. and Fairburn, C.G., The development and validation of the body shape questionnaire, Int. J. Eating Disord., 6 (1987) 485–494. De Bellis, M.D., Casey, B.J., Dahl, R.E., Birmaher, B., Williamson, D.E., Thomas, K.M., Axelson, D.A., Frustaci, K., Boring, A.M., Hall, J. and Ryan, N.D., A pilot study of amygdala volumes in pediatric generalized anxiety disorder, Biol. Psychiatry, 48 (2000) 51–57. Ellison, Z., Foong, J., Howard, R., Bullmore, E., Williams, S. and Treasure, J., Functional anatomy of calorie fear in anorexia nervosa (Letter), Lancet, 352 (1998) 1192. Goebel, R., Khorram-Sefat, D., Muckli, L., Hacker, H. and Singer, W., The constructive nature of vision: direct
28
[9]
[10]
[11]
[12]
[13] [14]
[15]
G. Seeger et al. / Neuroscience Letters 326 (2002) 25–28 evidence from functional magnetic resonance imaging studies of apparent motion and motion imagery, Eur. J. Neurosci., 10 (1998) 1563–1573. Gordon, I., Lask, B., Bryant-Waugh, R., Christie, D. and Timimi, S., Childhood-onset anorexia nervosa: towards identifying a biological substrate, Int. J. Eating Disord., 22 (1997) 159–165. Gordon, C.M., Dougherty, D.D., Fischman, A.J., Emans, S.J., Grace, E., Lamm, R., Alpert, N.M., Majzoub, J.A. and Rauch, S.L., Neural substrates of anorexia nervosa: a behavioral challenge study with positron emission tomography, J. Pediatr., 139 (2001) 51–57. Gorman, J.M., Kent, J.M., Sullivan, G.M. and Coplan, J.D., Neuroanatomical hypothesis of panic disorder, revised, Am. J. Psychiatry, 157 (2000) 493–505. Hendren, R.L., De Backer, I. and Pandina, G.J., Review of neuroimaging studies of child and adolescent psychiatric disorders from the past 10 years, J. Am. Acad. Child Adolesc. Psychiatry, 39 (2000) 815–828. Herholz, K., Neuroimaging in anorexia nervosa, Psychiatry Res., 62 (1996) 105–110. Irwin, W., Davidson, R.J., Lowe, M.J., Mock, B.J., Sorenson, J.A. and Turski, P.A., Human amygdala activation detected with echo-planar functional magnetic resonance imaging, NeuroReport, 7 (1996) 1765–1769. LaBar, K.S., Gatenby, J.C., Gore, J.C., LeDoux, J.E. and
[16]
[17]
[18]
[19]
[20]
[21]
Phelps, E.A., Human amygdala activation during conditioned fear acquisition and extinction: a mixed-trial fMRI study, Neuron, 20 (1998) 937–945. Lang, P.J., Bradley, M.M., Fitzsimmons, J.R., Cuthbert, B.N., Scott, J.D., Moulder, B. and Nangia, V., Emotional arousal and activation of the visual cortex: an fMRI analysis, Psychophysiology, 35 (1998) 199–210. Phillips, M.L., Young, A.W., Scott, S.K., Calder, A.J., Andrew, C., Giampietro, V., Williams, S.C., Bullmore, E.T., Brammer, M. and Gray, J.A., Neural responses to facial and vocal expressions of fear and disgust, Proc. R. Soc. Lond. B Biol. Sci., 265 (1998) 1809–1817. Rauch, S. and Shin, L., Functional neuroimaging studies in posttraumatic stress disorder, In R. Yehuda and A.C. McFarlane (Eds.) , Psychobiology of posttraumatic stress disorder. New York Academy of Sciences, New York, 1997, pp. 83–98. Seeger, G. and Lehmkuhl, G., Hirnelektrische Korrelate der Verarbeitung Affektiver versus Neutraler Reize bei Jugendlichen mit Anorexia Nervosa, Springer–Verlag, Berlin, 1993, pp. 375–379. Smeets, M.A., Body size categorization in anorexia nervosa using a morphing instrument, Int. J. Eating Disord., 25 (1999) 451–455. Talairach, J. and Tournoux, P., Co-planar Stereotactic Atlas of the Human Brain, Georg Thieme Verlag, Stuttgart, Germany, 1988.