Males and females differ in brain activation during cognitive tasks
Introduction
It has long been recognized that males and females exhibit differential performance on various cognitive tasks, including tests of visual–spatial and verbal domains (Kimura, 1996, Wegesin, 1998). Moreover, males and females experience different propensities for the development of neuropsychiatric disorders, may report different symptom profiles clinically, and present with altered levels of functioning and comorbidity (Kessing, 2004, Marneros et al., 2004, Winkler et al., 2004, Riecher-Rossler and Hafner, 2000, Weinstock, 1999, Endicott, 1998). These differences may reflect innate functional brain differences between the genders.
Sexual dimorphism of cognitive ability has consistently been shown to occur in two domains; in tests of spatial ability (mental rotation and spatial perception) where men outperform women and in tests of verbal ability (particularly verbal fluency), where women outperform men (Wegesin, 1998). Thus, most studies suggest that females perform better than males in tasks of verbal fluency, manual speed (i.e. finger tapping), and verbal and item memory, while males perform better than females in visuospatial tasks such as mental rotation, spatial rotation, and mathematical tasks (for full review see Kimura, 1996).
Previously, functional asymmetries in cerebral organization between males and females have been observed using positron emission tomography (PET) and single photon emission computed tomography (SPECT) in the study of cerebral metabolic rate and resting state cerebral blood flow, respectively (Li et al., 2004, Kastrup et al., 1999, Gur et al., 1995, Gur and Gur, 1990, Rodriguez et al., 1988). In general, this research seems to suggest that females have a higher regional cerebral blood flow than males (Kastrup et al., 1999). More recently, functional imaging studies, including functional magnetic resonance imaging (fMRI) studies, have been conducted to investigate gender influence upon regional brain activity changes and regional cerebral blood flow changes occurring during stimulus presentation. Tasks of mental rotation, visual stimulation, emotional recognition, verbal processing, and object construction have all shown significant patterns of differential activation between the sexes (Fischer et al., 2004, Lee et al., 2002, Lee et al., 2005, Weiss et al., 2003, Georgopoulos et al., 2001, Cowan et al., 2000, Ragland et al., 2000, Speck et al., 2000, Levin et al., 1998, Shaywitz et al., 1995). Gender-specific alterations in brain activation have been observed (across the various paradigms) in insular and thalamic regions (Lee et al., 2002, Lee et al., 2005), occipital and cingulate regions (Fischer et al., 2004, Lee et al., 2002), frontal regions (Lee et al., 2002), parietal regions (Weiss et al., 2003), and temporal regions (Ragland et al., 2000), as well as altered lateralization between the hemispheres (Lee et al., 2002, Georgopoulos et al., 2001, Speck et al., 2000, Levin et al., 1998, Shaywitz et al., 1995). Despite the general consensus that suggests differences between males and females, not all studies have found a significant gender effect (Schlosser et al., 1998). Excluding those fMRI studies which have employed emotional paradigm challenges (for which results are dependent on several factors including the emotion induced, the modality of the paradigm as well as gender specifics of the induced emotion), other studies suggest that females have greater bilateral activation during a phonological language task (Shaywitz et al., 1995), and greater lateralization to the left hemisphere during a working memory task (Speck et al., 2000). Additionally, females have demonstrated more frontal activation, compared to more parietal activation in males, during a mental rotation task (Weiss et al., 2003), and males have demonstrated a greater bias towards right hemisphere activation (and females to left hemisphere activation) during a task requiring a judgement of a whole object from its parts (Georgopoulos et al., 2001). Finally, females have also demonstrated a greater bilateral regional cerebral blood flow in temporal regions during performance of the Wechsler Memory Scale for memory recall (Ragland et al., 2000).
While some of the cognitive paradigms have demonstrated gender biases in terms of performance (females perform more accurately (although slower) on working memory task (Speck et al., 2000)) and on memory recall (Ragland et al., 2000), others have not (verbal test of orthographic, semantic, and phonological processing; Shaywitz et al., 1995; visuospatial test of mental rotation; Weiss et al., 2003).
The idea of teasing out gender effects in brain activation is difficult when we know that previous neuropsychological evidence supports gender-specific performance abilities in males and females on a variety of cognitive domains. For this reason, it is important to try and understand the possible relationships between gender, cognitive performance, and brain activation. In fact, findings from a recent study by Unterrainer et al. (2005) have shown both sex-specific and individual task performance-specific influences upon regional brain activity during a planning task.
Using the blood–oxygen-level-dependent (BOLD) response, we have assessed differences in regional brain activation in a group of male and female healthy volunteers over a variety of cognitive domains; verbal fluency, spatial attention, working memory, and motor tasks. Our hypotheses were first, that males and females would differ in brain activation patterns during spatial attention (for which males outperform females) and during verbal fluency (where females outperform males) but not necessarily during a motor task or in working memory performance where neuropsychological data do not support sexual dimorphism. In conjunction to this, we hypothesized that gender differences in cognitive performance on the tasks would be reflected by gender differences in the same direction on measures of brain activation. Thus, females would demonstrate a greater activation during the verbal task; males during the spatial attention task and both genders would show equivalent brain activity during the motor tasks. We did not make any hypothesis regarding the direction that either findings of performance or brain activation during the working memory task might take, although Speck et al. (2000) have demonstrated increased left hemisphere lateralization in females in this domain.
Section snippets
Subjects and study design
The ethics board of the University of Alberta Hospital approved this study.
Results
Thirty-three subjects participated in the study. There were no significant differences between these groups in terms of age (mean age ± SEM; males 26.7 ± 1.5, females 25.2 ± 2.0). One male subject failed to complete the baseline word generation paradigm. This subject was excluded from the analysis for this task.
Discussion
The present study demonstrates specific task-dependent effects of gender on both cognitive performance and on brain activation as measured by both BOLD signal extent and change in the number of pixels. Interestingly, however, our initial hypotheses were not upheld. While we found that males and females did indeed differ in brain activation patterns on several cognitive tasks (but not necessarily on those that we had hypothesized), we found that differences in cognitive performance were not
Acknowledgments
This work was supported in part by peer-reviewed grants from the Canadian Institutes of Health Research (CIHR) and the Alberta Heritage Foundation for Medical Research (AHFMR).
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