حافظه کاری برای عبارات عاطفی چهره : نقش استروژن در زنان جوان

Summary Physiological hormonal fluctuations during the menstrual cycle, postpartum, and menopause have been implicated in the modulation of mood, cognition, and affective disorders. Taking into account that women's performance in memory tasks can also fluctuate with circulating hormones levels across the menstrual cycle, the cognitive performance in a working memory task for emotional facial expressions, using the six basic emotions as stimuli in the delayed matching-to-sample, was evaluated in young women in different phases of the menstrual cycle. Our findings suggest that high levels of estradiol in the follicular phase could have a negative effect on delayed matching-to-sample working memory task, using stimuli with emotional valence. Moreover, in the follicular phase, compared to the menstrual phase, the percent of errors was significantly higher for the emotional facial expressions of sadness and disgust. The evaluation of the response times (time employed to answer) for each facial expression with emotional valence showed a significant difference between follicular and luteal in reference to the emotional facial expression of sadness. Our results show that high levels of estradiol in the follicular phase could impair the performance of working memory. However, this effect is specific to selective facial expressions suggesting that, across the phases of the menstrual cycle, in which conception risk is high, women could give less importance to the recognition of the emotional facial expressions of sadness and disgust. This study is in agreement with research conducted on non-human primates, showing that fluctuations of ovarian hormones across the menstrual cycle influence a variety of social and cognitive behaviors. Moreover, our data could also represent a useful tool for investigating emotional disturbances linked to menstrual cycle phases and menopause in women.

1. Introduction The sex steroid hormone estrogen affects the nervous system in many different ways extending beyond the role it plays in controlling the reproductive function. Recent studies have underlined several important issues regarding its hormonal influence on cognitive functions such as learning and memory processes (Stevens et al., 2005, Lacreuse, 2006, Luine, 2007 and Markou et al., 2005). This effect can be explained by the modulator role of estrogens on several neurotransmitter systems, acetylcholine in particular (Dumas et al., 2006 and Norbury et al., 2007), but also catecholamines (Leranth et al., 2000), serotonin (Bethea et al., 2002 and Amin et al., 2006a), and GABA, both in animals and in humans (McEwen, 2002, Sherwin, 2003 and Amin et al., 2006b). Another reason may lie in the widespread presence of estrogen receptors detected in many limbic regions involved in learning and memory, including the hippocampal formation and amygdala, and the cerebral cortex (Shughrue and Merchenthaler, 2000, Sherwin, 2003, Sherwin, 2006 and Markou et al., 2005). Due to the fact that estrogen acts across a broad range of neural systems, it is likely that it exerts its actions on cognition by altering the relative participation of specific memory systems, thus acting as a conductor, orchestrating the dynamics, timing and coordination of multiple cognitive strategies during learning (Korol, 2004 and Zurkovsky et al., 2007). In particular, the results of many studies suggest that estrogen enhances performance in working memory tasks, including face-tasks and the delayed matching-to-sample task (DMTS) (Lacreuse et al., 2000, Lacreuse et al., 2002, Lacreuse et al., 2007 and Lacreuse and Herndon, 2003). Taking into account that estrogen modulates cognitive processes, menstrual-cycle-related changes in estrogen levels can have different effects on various cognitive tests. In fact, in the late follicular and midluteal phases, compared to menses, improved performance on tests of articulatory and fine motor skills were reported while impaired performance on tests of spatial ability were revealed, indicating that variations in estradiol levels may, at least in part, be responsible for these effects (Hampson, 1990a, Hampson, 1990b, Hausmann et al., 2000 and Sandstrom and Williams, 2004). Numerous studies assessing performance across the estrous and menstrual cycles evidenced that ovarian hormones influence cognition and neural substrates subserving learning and memory, including working memory, in both rodents (Warren and Juraska, 1997, Daniel et al., 2006 and Kritzer et al., 2007) and humans (Hampson, 1990a, Hampson, 1990b and Janowski et al., 2000). The decline of estrogen levels after ovariectomy or menopause enhances the risk of diseases like osteoporosis and vasomotor dysfunction (Timins, 2004 and Warren and Halpert, 2004), but could also be involved in cognitive impairments (Sherwin, 2003 and Markou et al., 2005). Estrogen replacement therapy relieves various menopausal symptoms, but whether its benefits include comprised protection of cognitive functions is still controversial (Norbury et al., 2004, Resnick et al., 2004, Prelevic et al., 2005 and LeBlanc et al., 2007). The most consistent results are related to the positive cognitive effects of estrogen replacement therapy on verbal memory (Sherwin and Tulandi, 1996, Amin et al., 2006a and Stephens et al., 2006). Physiological fluctuations in sex hormones across the menstrual cycle allow for non-invasive studies of the cognitive effects of estrogen in young women and underlie a reliable pattern of cognitive modification across the menstrual cycle (Penton-Voak and Perrett, 2000, Lacreuse et al., 2001 and Maki et al., 2002). In order to point out possible differences related to the physiological hormonal fluctuations, in the present study the cognitive performance in a working memory task for emotional facial expressions, using six basic emotions (Ekman and Friesen, 1971) as stimuli in (DMTS), was evaluated in young women in the different phases across the menstrual cycle.

. Results 3.1. Hormonal levels Estradiol and progesterone levels in subjects in follicular and luteal phases were obtained by interpolation of data, utilizing a logarithmic linear regression straight line. The mean ± S.E.M. of estradiol levels in follicular and luteal phase were 5.41 ± 0.21 and 4.87 ± 0.12, respectively. Statistical comparison between the two phases showed a significant difference [t (40) = 2.146, p < 0.04]. The mean ± S.E.M. of progesterone levels in follicular and luteal phase were 80.67 ± 14.03 and 126.71 ± 22.38, respectively. 3.2. The DMTS task 3.2.1. Wrong answers, no answers and time of answer The subject performance in the DMTS working memory task with emotional stimuli varied across the three menstrual phases. As shown in Fig. 2, during the follicular phase the number of errors (wrong answers) significantly differed compared to those of the menstrual phase, [F(1,33) = 5.347, p < 0.03]. The number of errors in the luteal phase did not show any significant difference compared to both menstrual [F(1,33) = 1.010; p = 0.322, n.s.] and follicular phase [F(1,40) = 3.715; p = 0.061, n.s.]. Mean number (±S.E.M.) of wrong answers during menstrual phase (MP), follicular ... Figure 2. Mean number (±S.E.M.) of wrong answers during menstrual phase (MP), follicular phase (FP) and luteal phase (LP). The difference between MP and FP was statistically different (p < 0.03). LP did not show any significant difference compared to both MP and FP. Figure options In the follicular phase, subjects showed a significant difference in the number of “no answers” compared to the luteal phase, [F(1,40) = 4.182, p < 0.05] ( Fig. 3). No significant differences were found between menstrual phase and both follicular [F(1,33) = 2.43; p = 0.09, n.s.] and luteal phase [F(1,33) = 1.03; p = 0.343, n.s.]. Mean number (±S.E.M.) of “no answers” in MP, FP and LP. The difference between ... Figure 3. Mean number (±S.E.M.) of “no answers” in MP, FP and LP. The difference between FP and LP was statistically different (p < 0.05). No significant differences were found between MP and both FP and LP. Figure options Regarding the time employed to respond, subjects in the luteal phase were more rapid compared to those in the follicular phase, [F(2,53) = 9.187, p < 0.001] ( Fig. 4). Mean response time (±S.E.M.) in MP, FP and LP. The difference between FP and LP ... Figure 4. Mean response time (±S.E.M.) in MP, FP and LP. The difference between FP and LP was statistically different (p < 0.001). No significant differences were found between MP and both FP and LP. Figure options Taken together, these data suggest that high levels of estradiol in the follicular phase could have a negative effect on DMTS working memory task, using stimuli with emotional valence. To test this hypothesis, the performance relative to the emotional valence of stimuli was analyzed during the three phases of the menstrual cycle. 3.2.2. Emotional valence of stimuli The results obtained showed that the rate of errors in the follicular phase was significantly higher compared to the menstrual phase, in the facial expression of sadness, [F(2,53) = 3.00, p < 0.04] and disgust, [F(2,53) = 4.393, p < 0.02] ( Fig. 5). Mean number (±S.E.M.) of wrong answers during MP, FP and LP, with regard to ... Figure 5. Mean number (±S.E.M.) of wrong answers during MP, FP and LP, with regard to emotional valence of facial expressions. H: happiness; SU: surprise; SA: sadness; F: fear; A: anger; D: disgust. The rate of errors in FP was significantly higher compared to MP, for the facial expressions of sadness (p < 0.04) and disgust (p < 0.02). Figure options No significant differences were found between the two phases in terms of “no answers” rates related to the emotional valence of the stimuli (Fig. 6). Mean number (±S.E.M.) of “no answers” in MP, FP and LP, with regard to emotional ... Figure 6. Mean number (±S.E.M.) of “no answers” in MP, FP and LP, with regard to emotional valence of facial expressions. H: happiness; SU: surprise; SA: sadness; F: fear; A: anger; D: disgust. The difference among the different cycle phases was not statistically significant for any of the facial expressions. Figure options The analysis of the response times for each facial expression with emotional valence showed a significant difference between follicular and luteal phase, relative to the expression of sadness, [F(2,445) = 3.29, p < 0.002] ( Fig. 7). Mean response time (±S.E.M.) in MP, FP and LP, with regard to emotional valence ... Figure 7. Mean response time (±S.E.M.) in MP, FP and LP, with regard to emotional valence of facial expressions. H: happiness; SU: surprise; SA: sadness; F: fear; A: anger; D: disgust. The difference between FP and LP was statistically different (p < 0.002), relative to sadness.