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Psychosomatic Medicine 66:132-140 (2004)
© 2004 American Psychosomatic Society

ORIGINAL ARTICLES

Alexithymia Correlates With the Size of the Right Anterior Cingulate

Harald Gündel, MD, Anna López-Sala, PhD, Andres O. Ceballos-Baumann, MD, PhD, Joan Deus, PhD, Narcís Cardoner, MD, Birgit Marten-Mittag, MS, Carles Soriano-Mas, PhD and Jesús Pujol, MD

Institut für Psychosomatische Medizin (H.G., B.M.-M.), TU München; Magnetic Resonance Center of Pedralbes (A.L.-S., C.S.-M., J.P.), Barcelona; Hospital of Mataró (J.D.), Barcelona; Hospital of Bellvitge (N.C.), University of Barcelona; Neurologische Klinik und Poliklinik (A.O.C.-B.), Klinikum rechts der Isar, TU München.

Address correspondence and reprint requests to Dr. Harald Gündel, Institut und Poliklinik für Psychosomatische Medizin, Psychotherapie und, Medizinische Psychologie, TU München, Klinikum rechts der Isar, Langerstr. 3, D - 81675 München. E-mail: H.Guendel{at}lrz.tu-muenchen.de


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 NOTES
 ACKNOWLEDGMENTS
 REFERENCES
 
OBJECTIVE: The authors investigated a possible relationship between interindividual variability in anterior cingulate gyrus (ACG) morphology and alexithymia.

MATERIALS AND METHODS: Magnetic resonance images were obtained in 100 healthy university graduates (51 female, 49 male; mean age 25.6 y). Surface area measurements of the ACG were performed on reformatted sagittal views in both hemispheres. The Toronto Alexithymia Scale (TAS-20) and the Temperament and Character Inventory (TCI) were administered.

RESULTS: Right ACG surface area significantly correlated with TAS-20 total score in men (r = 0.37; p = 0.009) and in women (r = 0.30; p = 0.034). After controlling for three TCI subscales (harm avoidance, self-directedness, and self-transcendency), the correlation between TAS-20 total and right ACG became nonsignificant in women, but was only slightly reduced (r = 0.32; p = 0.032) in men. A linear regression model with right ACG as a dependent variable revealed brain volume, TCI-harm avoidance and TAS 20 total score as significant predictors in the total sample (explained proportion of total variation (EPTV) 37%). In men, beside brain volume, only TAS-20 total score showed a highly significant contribution (EPTV 41%), whereas in women only TCI-harm avoidance was a significant predictor (EPTV 36%).

CONCLUSIONS: The authors’ findings indicate that there is a significant positive relation between the size of the right ACG and alexithymia as measured with the TAS in healthy subjects. This applies especially for men whereas in women ACG size is more associated with the subscale harm avoidance of the TCI. Our findings also suggest a partial lateralization of human emotion processing, especially negative emotion.

Key Words: alexithymia, • anterior cingulate, • emotion processing, • lateralization, • personality.

Abbreviations: ACG = anterior cingulate gyrus;; ACC = anterior cingulate cortex;; TAS-20 = Toronto Alexithymia Scale, 20-item version;; TCI = Temperament and Character Inventory;; HA = TCI subscale harm avoidance;; SD = TCI subscale self-directedness;; ST = TCI subscale self-transcendence;; BA = Brodmann’s area;; MRI = magnetic resonance imaging;; PET = positron emission tomography;; CSF = cerebrospinal fluid;; CBF = cerebral blood flow;; CNS = central nervous system;; PTSD = posttraumatic stress disorder;; THC = tetra-hydro-cannabinol.; EPTV = explained proportion of total variation.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 NOTES
 ACKNOWLEDGMENTS
 REFERENCES
 
Alexithymia (from the Greek "a" for lack, "lexis" for word, and "thymos" for emotion) refers to a specific disturbance in emotional processing that is manifested clinically by difficulties in identifying and verbalizing feelings, in elaborating fantasies, and by a tendency to focus on and amplify the somatic sensations accompanying emotional arousal. Nowadays, alexithymia is conceptualized as multifaceted and dimensional, rather than a categorical construct. Salient features are the inability to distinguish one’s feelings from the accompanying bodily sensations, the inability to communicate feelings to others, and an externally orientated cognitive style reflecting an absence of inner thoughts and fantasies. These three lower-order concepts reflect separate, yet empirically related, facets of the alexithymia construct (1).

Referring to the neurobiological basis of alexithymia, a structural/cerebral deficit was hypothesized as early as in the end of the 1970s. MacLean (2) inferred that the limbic system ("visceral brain") functions as a crude analyzing mechanism that derives information and interprets experience in terms of emotional states instead of symbolic thoughts (3). He further speculated that, instead of being related to the neocortex (which he referred to as the "word brain"), distressing emotions find immediate expression through autonomic pathways (4). Nemiah suggested a neurophysiological dysfunction, caused by a "lack of adequate neuronal connections" between limbic system and neocortex (5). Theories further evolved from Nemiah’s "vertical" model to a "horizontal" model. Hoppe and Bogen (6) observed a paucity of fantasies, difficulty in describing feelings, and an operative style of thinking in 12 "split-brain" individuals (ie, patients who had undergone cerebral commissurotomies for treatment of intractable epilepsy). Thus Hoppe assumed a "functional commissurotomy" in alexithymia (6). Numerous studies were then conducted, hypothesizing a hemispheric specialization (7–10) and/or an interhemispheric transfer deficit in alexithymia (6,8,11–19).

This deficit could apply particularly to men, as was suggested by a study showing that among men, alexithymic deficits in the ability to identify or describe feelings were related to both a relative impairment in the functioning of the right hemisphere and an impairment in the ability to transfer information between cerebral hemispheres. In contrast, women exhibited less hemisphericity and appeared to be more bilaterally organized (20), suggesting that the neurobiological substrate of alexithymia may be different in men and women.

In addition, some studies have explored the relationship between alexithymia and personality traits. Two studies found a positive correlation between alexithymia and neuroticism and a negative correlation with openness and extraversion (21,22). The correlations with the temperament and character dimensions and subscales described within Cloninger’s empirically confirmed psychobiological model of personality (23) have also been studied. Thus, in a recent study including 254 psychiatric inpatients and outpatients, the temperament and character inventory (TCI) dimensions harm avoidance, low self-directedness, and low reward dependence were found to be independent predictors for alexithymia (24). These personality traits may contribute to the characterization of high alexithymic patients as experiencing predominantly poorly differentiated emotional distress because they lack the necessary psychological capacities for modulating emotions (25). In recent years, several personality theorists have emphasized the need for linking personality constructs with neurobiological processes that might underlie individual differences in personality (3).

The anterior cingulate cortex (ACC) has classically been related to affect (26) and is part of a circuit involved in a form of attention that serves to regulate emotional processing (2–30). However, in addition to emotion, the ACC is now recognized to play important roles in attention processing, pain, response selection, maternal behavior, skeletomotor function, and autonomic control (31). Convergent data suggest that the ACC is functionally divided into two major subdivisions that subserve distinct functions, ie, a dorsal cognitive part (BA areas 24b’-c’ and 32') and a rostral–ventral affective part (BA areas 24a-c and 32, ventral areas 25 and 33) (32). There is some evidence suggesting that the rostral ACC serves a more exclusively emotional function, whereas the dorsal ACC appears to serve a superordinate function that may be greatly influenced by, but is not exclusively dedicated to, emotional processing. Lane (33) considered the possibility that both of these areas of the ACC are participating in different aspects of conscious emotional experience. He hypothesized that the dorsal ACC may reflect phenomenal awareness (direct experience) of emotion. In keeping with this, a PET study showed that individual differences in the ability to accurately detect emotional signals interoceptively or exteroceptively was a function of the right dorsal ACC (BA 24) (34, 35). In contrast, the rostral ACC (together with the medial prefrontal cortex) may participate in cognitive operations performed on the contents of phenomenal experience of emotion, ie, in reflective awareness of emotion or "knowing how one is feeling" (33). Thus, the tight anatomical linkage (33) between the rostral and dorsal anterior cingulate cortices may be the anatomical basis for generating the interaction between the phenomenal experience of emotion and establishing and elaborating on the representations of that emotional experience (33).

On the basis of the findings that: (1) emotional awareness is negatively correlated with alexithymia; (2) emotional awareness is correlated with blood flow in the ACC during emotion; and (3) the ACC is one of those structures involved in emotional experience. Lane et al. hypothesized alexithymia as a deficit in the conscious awareness of emotion that would be associated with a circumscribed, strategically located deficit in the anterior cingular cortex activation during emotional arousal, and proposed to conceptualize alexithymia as the emotional equivalent of blindsight (34). This "blindfeel" hypothesis therefore introduces the possibility that the sensory component of attention, ie, the spotlight of consciousness, is another essential function of the ACC, and that the ACC could thus mediate conscious attention to both "cognitive" and "emotional" stimuli.

There is growing evidence that variations in the morphology of the ACC reflect underlying functional anatomy (36–38). Interestingly, Good et al. (39) used voxel-based morphometry to examine the MRI exams of 465 normal subjects and found left-predominant asymmetry for the anterior cingulate sulcus and right-predominant asymmetry for the anterior cingulate gyrus. Moreover, females had significantly more gray matter volume within the right cingulate gyrus than males. Summarizing these data and our own results (40) suggests that the right cingulate gyrus is larger than the left, particularly in women.

In addition, in a previous article linking cingulate measurements to personality constructs (four temperament and three character dimensions of the TCI), our group found a significant positive correlation between surface measurements of the right anterior cingulate gyrus and the character dimension "harm avoidance" in both sex groups (40).

In the present study we tested the hypothesis that alexithymia may also have a structural substrate in that interindividual variability in ACG morphology correlates with the Toronto-Alexithymia-Scale (TAS-20). Specifically, the primary hypothesis of the study was that the surface area of the right ACG is negatively correlated with the TAS-20 score.

As secondary hypothesis, we expected that right ACG and TAS-20 are more correlated in men than in women.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 NOTES
 ACKNOWLEDGMENTS
 REFERENCES
 
Subjects
Recruited volunteers included 100 healthy subjects, with 51 women and 49 men between ages 20 and 43 years. This sample overlaps partly with a sample described elsewhere (40). Recruitment was individually performed by university teachers in the university environment of Barcelona with no payment offered. The subjects were screened for a positive history of neurological, psychiatric, and serious medical disorders, as well as for alcohol and drug abuse.

Mean age for the total sample was 25.6 (SD 4.2) years and was 25.5 (SD 3.6) years for women and 25.8 (SD 4.8) years for men. All selected participants were white residents from Barcelona and all were in final year of university or graduates. According to the Edinburgh Handedness Inventory (41) 91) subjects had a right-hand preference and 9 subjects had a left-hand preference. After a complete description of the study to the subjects, written informed consent was obtained.

Alexithymia and Personality Assessment
A validated Spanish translation using back-translation methodology (42) of the 20-item TAS-20 was applied in this study as a screening device for measuring alexithymia. The TAS-20 is the most widely used and validated alexithymia measure. In this study, the total score was analyzed, as well as the score of the three facets: factor 1 (f1; difficulty identifying feelings); factor 2 (f2; difficulty describing feelings); factor 3 (f3; externally orientated thinking). We analyzed these scores as continuous dimensions rather than by comparing extreme groups.

Additionally, a validated Spanish translation (43) of the 240-item Temperament and Character Inventory (TCI) version 9 (44) was used in this study. This questionnaire produces separate scores for four temperament and three character dimensions. The four temperament dimensions novelty seeking (NS), harm avoidance (HA), reward dependence (RD), and persistence (PS) are thought to determine predominantly inherited automatic emotional responses that can already be observed early in life. These dimensions involve preconceptual biases in perceptual memory and habit formation toward external and internal stimuli (45,46). Contrary to the temperament dimensions, the character dimensions self-directedness (SD), cooperativeness (CO), and self-transcendence (ST) are thought to develop with the maturing self-concept in adulthood, influencing personal and social style by insight learning (24). All dimensions, except persistence, have three to five lower-order subscales. Within this context, harm avoidance reflects a tendency to respond intensely to aversive stimuli and involves anticipatory worry about possible problems, fear of uncertainty, shyness with strangers, and consequent easy fatigability. People with a high score in harm avoidance are described as pessimistic, worrisome, fearful, fatiguing, and shy.

MRI Examination
The imaging data were acquired using a 1.5 T magnet (Signa, GE Medical Systems, Milwaukee, WI). A 60-slice three-dimensional (3D) spoiled gradient recalled acquisition in the steady-state sequence was obtained in the sagittal plane. Acquisition parameters were TR 40 ms, TE 4 ms, pulse angle 30°, field of view 26 cm, and matrix size 256 x 192 pixels. Section thickness varied according to the brain size, ranging from 2.4 to 2.6 mm.

The first phase of image analysis was performed on an auxiliary workstation (SPARCstation 20; Sun Microsystems, Mountain View, CA) using commercially available software (Advantage Windows, version 2.0; GE Medical Systems) and adapting procedures used previously (47). A 3D MRI model of each subject’s head was constructed and reformatted to high-resolution 1-mm slices. Axial views of the reformatted MRI were used to identify the plane of the interhemispheric fissure and to select two oblique sagittal images that optimally exposed left and right medial brain surfaces. Finally, each oblique sagittal image was coded and stored with no reference to the subject’s name, age, sex and hemisphere.

To obtain cerebral volume measurements, a 3D surface rendering of each subject’s brain was built by isolating neural tissue from the surrounding CSF using volume segmentation tools (47). The analysis system directly provided the volume (ml) of the entire brain after its isolation in each subject.

In a second phase, reformatted sagittal views were interpolated to a high-resolution matrix (512 x 512 pixels) to perform the surface measurements. A general software for image analysis was used (Image-Pro plus; Media Cybernetics, Silver Spring, MD). Two cingulate regions were manually traced on each hemisphere according to the individual sulcal patterns (Figure 1) and measured in mm2. The anterior region corresponded to the anterior cingulate gyrus. The posterior cingulate region included the posterior cingulate gyrus and the medial parietal cortex (precuneus). The border between anterior and posterior cingulate regions was established at the midpoint between anterior and posterior commissures, which approximates the boundary between BA areas 24 and 23 (36, 48, 49).



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  		Figure 1. Region delimitation adopted in this study. The anterior cingulate gyrus appears shaded darker than the posterior cingulate region. The arrow of the left picture indicates the presence of a second cingulate sulcus delimiting a paracingulate gyrus that was not included in our region of interest. The arrow in the right picture points to an intralimbic sulcus within the cingulate gyrus. Note the large difference in the extent of the anterior cingulate gyrus in these two subjects.

 
An asymmetry index (50) was computed for both cingulate regions according to the expression 100 * (L - R)/(L + R), in which L and R were measurements for the left and right hemispheres. This index is identical to that used by Paus et al. (48). In accordance with these authors, an absolute value of 5% was considered as the minimum level of asymmetry. This corresponds to the 0.1 asymmetry index values of Galaburda et al. (51) and is conventionally used to compare anatomical asymmetries from different studies (52). Asymmetrical cases, therefore, were those showing values less than -5 (right-side pattern) or more than +5 (left-side pattern).

The measurements were performed by a researcher blind to the subject’s age and sex and to any reference identifying brain hemisphere (images from both hemispheres were presented with identical left–right orientation). The reproducibility of measurements proved to be good. Intraclass correlation coefficient of 0.92 was obtained for 100 surface measurements of the right anterior cingulate gyrus repeated after 2 weeks. To assess interrater reliability, a second researcher measured this region in a subsample of 40 randomly chosen cases also in blind conditions. The intraclass correlation coefficient between the two raters was 0.91.

Statistical Analysis
SPSS for Windows, version 10.0, was used for statistical analysis. Sex differences in anatomical data (Table 1) were tested with t tests for independent samples or with ANCOVAs. Asymmetry index rates between anterior and posterior cingulate regions and between sexes were compared with {chi}2 tests. To assess the effects of sex and hemisphere and their interaction on cingulate region surface areas, a repeated measures ANCOVA was performed with hemisphere as a within subjects factor, sex as a between subjects factor and brain volume as a covariate. Sex differences in psychometric data were assessed with a t test for TAS-20 total score, and with a repeated measures ANOVA for the single facets, with sex as a between subjects, and the three facets as within subjects factors. Correlations between TAS-20 and cingulate region surface areas and between TAS-20 and TCI-scores were presented as bivariate or partial Pearson’s product-moment correlation coefficients. Finally, multiple linear regression analysis with right ACG as dependent variable was used to assess the predictive power of TAS-20 total score controlling for several possible confounders. For variable selection we used forward method with the entry criterion p < 0.05.


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  		TABLE 1. Summary of Anatomical Results
 

   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 NOTES
 ACKNOWLEDGMENTS
 REFERENCES
 
Anatomical Analysis
Table 1 summarizes the anatomical data for the study population. Referring to the raw mean, men showed a slightly larger right ACG than women, although differences were not statistically significant. In contrast, after controlling for brain volume, women showed a larger right ACG than men (F = 5.64; df = 1, 97; p < 0.05) (Table 1). For the left ACG and for the posterior cingulate region, no sex differences were significant after adjusting for brain volume.

It has been observed that hemispheric asymmetry for ACG is very frequent. In 83% of subjects the asymmetry index for this brain region was less than -5 or more than 5. In contrast, the posterior cingulate region was asymmetrical in only 29% of subjects. This regional difference in the frequency of hemispheric asymmetry was significant at {chi}2 = 59.2 and p < 0 0.001. Inspection of Table 1 shows that the distribution of asymmetry patterns for the anterior cingulate gyrus was not quite the same in both sexes. However, this difference was not statistically significant.

This asymmetrical pattern of the ACG surface area was further confirmed by means of a repeated measures model with hemisphere as a within–subject factor, sex as a between-subject factor, and total brain volume as covariate, which revealed a significant effect of hemisphere (right > left) (F = 10.3; df = 1, 98; p < 0.01). Although hemisphere multiplied by sex interaction was not significant (F = 0.7; df = 1, 98; p = 0.404), post hoc comparisons showed that the right anterior cingulate gyrus was significantly larger than the left only in women (F = 8.9; df = 1, 49, p < 0.01). Men, however, showed no significant difference in hemispheres (F = 2.6; df = 1, 48, p = 0.113).

Psychometric Analysis
Table 2 provides alexithymia scores measured with the TAS-20 scale and the scores for each of the subscales for the total sample and for men and women separately. Mean TAS-20 total score was 39.38 (SD: 9.3; range: 24–60). According to the categorical approach of TAS-20 guidelines, 84% (N = 84) of the sample could be classified as within the nonalexithymic range (TAS-20 less than or equal to 51), and 16% (N = 16) scored greater than 51 but less than 61 (neither alexithymic nor nonalexithymic). Thus, none of the subjects was alexithymic by TAS-20 definition. The quartiles of the distribution of the TAS-20 score were 33 (25%), 37 (50%), and 44 (75%). The comparisons between sexes revealed that men scored higher than women in the total score of the TAS-20 (t = 2.28; df = 98; p < 0.05) and in factor 3 (externally orientated thinking) (t = 3.66; df = 98; p < 0.001).


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  		TABLE 2. Summary of Psychometric Data
 
Correlations Between Anatomical and Psychometric Data
Table 3 displays the correlations (controlled for total brain volume) between the extension of the four cingulate regions and the alexithymia scores for the total sample and for men and women separately. Only right ACG significantly correlated with TAS-20 total score in men (r = 0.37; N = 49; p < 0.01) and in women (r = 0.30; N = 51; p < 0.05).


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  		TABLE 3. Correlations Between AC/PC Surface Area and TAS-20 Total Score
 
With regard to the single facets of the TAS-20 scale, we found that correlations with right ACG differed between sexes (Table 4). While significant correlations were observed in men between right ACG and factor 1 (difficulty identifying feelings) (r = 0.40; N = 49; p < 0.01) and factor 2 (difficulty describing feelings) (r = 0.35; N = 49; p < 0.05); in women, only a nearly significant correlation was observed with factor 3 (externally orientated thinking) (r = 0.28; N = 51; p = 0.052).


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  		TABLE 4. Correlations Between TAS-20 Subscales and Right ACG
 
In a previous report (15), we have shown that right ACG surface area was related to harm avoidance, as measured by Cloninger’s TCI (19). In our sample TCI harm avoidance, TCI self-directedness and TCI self-transcendence scores were correlated to TAS-20 total score (TCI-HA: r = 0.21, p < 0.05; TCI-SD: r = -0.36, p < 0.01; TCI-ST: r = 0.22, p < 0.05). Thus we studied in how far these three TCI subscales may account for the observed correlation between TAS-20 total score and right ACG surface area.

Controlling for TCI-HA, TCI-SD, and TCI-ST has a differentiating effect depending on sex. In women, the correlation between TAS-20 total score and right ACG became nonsignificant (before controlling for TCI-HA, TCI-SD, TCI-ST: r = 0.30; N = 51; p < 0.05; controlling for TCI-HA, TCI-SD, TCI-ST: r = 0.09; N = 51;p = 0.566). On the contrary, in men, this same correlation was only slightly reduced after controlling for TCI-HA, TCI-SD, and TCI-ST (before controlling for TCI-HA, TCI-SD, TCI-ST: r = 0.37; N = 49; p < 0.01; controlling for TCI-HA, TCI-SD, TCI-ST: r = 0.32; N = 49; p < 0.05).

To further investigate the relationship between right ACG and TAS-20 total score and the possible confounding effects of the TCI dimensions, a linear regression model was applied to the total sample (N = 100) with right ACG as dependent variable. As predictor variables we included TAS-20 total score and the psychological subscales, which showed a significant correlation to TAS-20 total score in univariate analysis: TCI-HA, TCI-SD, TCI-ST. Controlling for brain volume and sex in a first block, we used forward selection of psychological variables from a second block. Only TCI-harm avoidance and TAS 20 total score met the entry criterion. From the first block brain volume showed a highly significant correlation to right ACG in this model (Table 5, model 1). We next examined the regression models in the two sexes separately. In men, beside brain volume, only TAS-20 total score showed a highly significant contribution, whereas in women only TCI-harm avoidance was a significant predictor. To see what happens to the TAS-20 and TCI-HA variables, we report the full model including TAS-20, TCI-HA and brain volume for both sexes (Table 5, models 2 and 3).1


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  		TABLE 5. Linear Regression Models with AC Right as Dependent Variable
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
NOTES
 ACKNOWLEDGMENTS
 REFERENCES
 
In contrast to our primary hypothesis, our findings indicate that there is a significant positive correlation between the size of the right anterior cingulate gyrus and alexithymia as measured with the 20-item TAS in healthy subjects. As hypothesized, this applies especially for men, whereas in a previous publication we already suggested that a prominent right anterior cingulate was associated with a tendency to withdrawal-related behavior (harm avoidance), especially in women (40). The relationship between the size of the right anterior cingulate gyrus and alexithymia in women observed in the present investigation seems to rely on what alexithymia and harm avoidance have in common.

Our results add further evidence to the findings from earlier studies which described different neurobiological patterns of high alexithymia in men vs. women. Lumley and Sielky (20) looked at the relationship of alexithymia and an impairment of the right hemisphere or a deficiency in interhemispheric transfer in a nonclinical sample of 47 college men and 58 college women. Using a tactile finger localization task, they calculated a hemisphere index to test the right hemisphere dysfunction hypothesis and a crossing index to test the interhemispheric transfer deficit hypothesis of alexithymia. Interestingly, among men, alexithymic deficits in the ability to identify or describe feelings are related to both a relative impairment in the functioning of the right hemisphere and an impairment in the ability to transfer information between cerebral hemispheres. In contrast, within the female sample, alexithymia and its facets are unrelated to the measures of hemispheric dysfunction (20). Additionally, Spalletta et al. (53) reported that men with a right-hemisphere stroke had a high level of alexithymia and were more alexithymic than those with a left-hemisphere stroke. In women, there was no difference between patients with a left-hemisphere and a right-hemisphere stroke, and both female subsamples had a high level of alexithymic features. We found a significant positive correlation between the size of the right anterior cingulate and alexithymia in male and in female university students. But only in men was this relationship maintained after controlling for HA, whereas this was not true in women.

Lane et al. (54) found some support for the hypothesis that the degree to which the right hemisphere participates in the processing of emotion-laden stimuli influences the degree to which emotional information is processed in a differentiated and complex manner. According to our findings, the ability to accurately detect emotional signals interoceptively or exteroceptively may indeed be a function of the right ACC (BA 24). This was suggested in a PET activation study by Lane et al. during film- and recall-induced emotion. These authors correlated regional cerebral blood flow (CBF) changes attributable to emotion with subjects’ scores on the Levels of Emotional Awareness Scale (LEAS), a measure of individual differences in the capacity to experience emotion in a differentiated and complex way (35). Correlations between LEAS scores (which is inversely correlated with alexithymia) and rCBF overlapped significantly in BA area 24 of the right anterior cingulate cortex.

A recent functional magnetic resonance imaging (fMRI) study investigated the neural response to emotional stimuli in a group of eight men with and eight men without alexithymia and hypothesized that, according to the blindfeel hypothesis (34), alexithymia would be associated with a deficit in the participation of the anterior cingulate cortex during emotional arousal (55). Indeed, negative high-arousal emotional stimuli induced less activation in the left mediofrontal-paracingulate gyrus in men with alexithymia than in those without alexithymia. Nothing can be said about the excitatory or inhibitory quality of anterior cingulate activation during this emotion-arousing paradigm. However, the decrease of activity in the rostral anterior cingulate cortex/mediofrontal cortex when viewing negative pictures might suggest that alexithymia is associated with a deficit in reflective awareness (ie, the mental representation of the current emotional state) of negative affect (55). Although this preliminary data are difficult to interpret in terms of laterality, the partially convergent findings of this study (fMRI study of alexithymic vs. nonalexithymic males) and our results provide further evidence that functional differences in ACC activation during emotional processing may be related to structural differences in this specific region.

How could we—in contrast to our primary hypothesis of a negative correlation between ACG surface area and TAS-20 total score—explain an increased size of particularly the right anterior cingulate surface area in high alexithymia? The right hemisphere is more efficient than the left in monitoring sensory inputs for alerting signals and mediating stimulus-triggered reactions (56, 57). In addition, Damasio suggests that the right somatosensory cortices are "dominant" with regard to integrated body mapping and therefore most important for generating emotions and feelings (58). Also, an asymmetrical (greater right than left) frontal activation is associated with emotional responses related to suppression of ongoing activity such as fear and disgust (59).

Characteristic alexithymic features, especially the suppression of traumatic memories and the conscious awareness of related feelings, have early been described in a subgroup of severe PTSD patients (60). Recently, dissociative PTSD patients, defined as showing no concomitant increase in heart rate while recalling a traumatic memory (ie, suppressing emotional arousal), showed greater activation than the control group specifically in the right anterior cingulate gyrus (BA 24 and 32) (61). This finding is somewhat consistent with the finding of increased global cerebral blood flow in the anterior cingulate gyrus following THC-induced depersonalization, another mode of dissociative processes (62). Dissociation is considered to serve as a defense mechanism against intolerable, trauma-associated memories and feelings, and results from a disintegration of consciousness, memory, identity and perception (63). In dissociation as well as in alexithymia, patients may have difficulties in integrating aspects of certain neuropsychological functions, namely memories and feelings, into current awareness. Indeed, several authors (63, 64) found a strong positive correlation between the TAS-20 total score, the subscores "difficulty identifying feelings" and "difficulty expressing feelings" and dissociative symptomatology. In accord with these findings, a recent study suggested the existence of an active inhibitory control mechanism which is likely to include the anterior cingulate and prevents the retention of unwanted memories when encountering a certain stimulus. This finding supports the notion of a suppression mechanism that pushes unwanted associations out of awareness (65), and may point to the possible existence of other active inhibitory mechanisms within cognitive and emotional processing as well. Thus our finding of a positive correlation between alexithymia and right ACG surface area could therefore neurobiologically represent a dysfunctional organization of an environmentally induced neuronal inhibitory system in the allocation of attentional resources especially toward (internal and external) emotional cues, particularly in men. This hypothesis is supported by our finding of a significant correlation between right ACG surface area and TAS-20 factor 1 (difficulty identifying feelings) Therefore, we speculate that the larger extent of right ACG surface area in higher alexithymia may represent the structural, neuroanatomical correlate of an active inhibitory system causing a down regulation of emotional processing during the exposition to experimental or expressive aspects of emotion.

There are some restrictions to our study. First, regarding the sex differences in our findings, alexithymia (66) is less pronounced in women and also in our cohort. It is therefore statistically more difficult to demonstrate a relationship between large anterior cingulate and alexithymia specifically for women. Secondly, we did not study psychiatric patients with alexithymia in a clinical sense but healthy young university graduates. Therefore our finding may relate to differences on the continuous scale of emotional intelligence rather than to clinically meaningful alexithymia. There clearly is an additional need for a similar study in clinical subjects. Thirdly, although alexithymia and depression are clearly distinct constructs (67), it is now well established that alexithymia is often associated with depression and trait anxiety (66,68). Honkalampi (66) found in a large epidemiological study that the prevalence of alexithymia was only 4.3% among nondepressed subjects, whereas, among the depressed subjects, the prevalence of alexithymia was higher by eight-fold (32%). Thus depression and trait anxiety are critical dimensions, particularly when studying the links between affective style and brain structure. Therefore another potential confounding factor of our study is that the correlations between alexithymia and right ACG surface area have not controlled for these dimensions. As we studied healthy young subjects, we assume a relatively low level of depression and anxiety within our sample. However, future studies should include the measurement of depression and trait anxiety by using appropriate anxiety and depression self-report questionnaires in conjunction with the TAS-20.

In conclusion, our data further contribute to the hypotheses that right anterior cingulate gyrus morphology significantly correlates with alexithymia as measured with the 20-item TAS and that there are sex-specific differences in emotional processing.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 NOTES
 ACKNOWLEDGMENTS
REFERENCES
 
The authors thank Montse Vall-llovera for her assistance in results assessment, and Mary-Frances O’Connor for her assistance in the preparation of the manuscript.


   NOTES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 NOTES
ACKNOWLEDGMENTS
 REFERENCES
 
1 Within the n = 9 left-handed subjects, right AC surface area (730.1 mm2) is smaller than left AC surface area (765.9 mm2), whereas we find the opposite asymmetry pattern in the n = 91 right-handed subjects (right AC: 931.0 mm2; left AC: 811.2 mm2). There is no significant difference in TAS-20 (39.7 vs. 36.3) or TCI-HA (52.5 vs. 49.2), TCI-SD (52.2 vs. 51.7), and TCI-ST (38.2 vs. 41.3) values between right- and left-handed people. In addition there is a positive correlation between right AC extent and TAS-20 score within the n = 9 left-handed subjects (r = 0.45, p = 0.261), the n = 91 right-handed subjects (r = 0.23, p = 0.027) and the whole sample (n = 100; r = 0.27, p = 0.006). Because it is unclear if the different asymmetry of the right versus left AC surface area in right- and left-handed people is caused by systematic or coincidental differences, and the correlations between AC extent and TAS-20 score are significant in the right-handed subjects as well as the whole sample, we have reported the results of the whole (n = 100) sample. Back

Received for publication November 10, 2002.

Revision received May 27, 2003.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 NOTES
 ACKNOWLEDGMENTS
 REFERENCES
 

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