How the brain puts the pieces together: Sex differences in integrative function
Rebecca J HamiltonŦ, Leanne M Williams*, Elkhonon Goldberg∫, Albert R HaigŦ *, Rubin C Gur‡, Raquel E Gur‡, Pierre Flor-Henry° and Evian GordonŦ * Ω
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Brain Resource International Database (The Brain Resource Company); Ultimo, NSW 2007, Australia The Brain Dynamics Centre, Westmead Hospital, NSW 2145; School of Psychology, University of Sydney, NSW 2006, Australia ∫ Department of Neurology, School of Medicine, New York University, New York, NY 10016, USA ‡ Section of Neuropsychiatry, Department of Psychiatry, University of Pennsylvania, Pennsylvania 19104, USA ° Department of Psychiatry, University of Alberta, Edmonton, Canada Ω Department of Psychological Medicine, University of Sydney, Australia
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Brain ResourceTM
Summary • Gamma (40 Hz) phase synchrony was recorded in 275 male and 275 female subjects during an auditory oddball task. • Results showed a marked sex dissociation in spatial and temporal cortical synchronization. • Females showed a bilateral gradient of frontal-posterior synchronization that was not present in males. • Males showed a frontal lobe lateralization that was absent in females. Rationale Hemispheric specialization appears to be greater in males, while females preferentially show bilateral activation.1 Coherent cognition requires activity across diverse brain networks to be brought together, and synchronous, inphase oscillations in the Gamma (40 Hz) range are thought to be one mechanism underlying this functional “integration” of brain networks.2 Previous research into sex differences in functional brain activity have often used lesioned subjects. The present study is the first to directly investigate sex differences in network recruitment in healthy subjects through a measure of cortical synchronization.
Results Frontal-posterior gradient of Gamma 1 synchrony evident in females (left) but not males (right).
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1A (Females)
Time (ms)
1B (Males)
Time (ms)
Lateralization of frontal Gamma 2 synchrony evident in males (right) but not females (left)
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Discussion •The patterns of synchronization observed reflect the preferential engagement of cortical networks involved in processing salient stimuli. •The observed sex differences in these patterns suggest different strategies for processing such stimuli in males compared to females. •An anatomical substrate may underpin this differentiation. Females are known to show a relatively larger corpus callosum compared to males,4 and this allows more bilateral network recruitment in the processing of salient stimuli. •Diffusion Tensor Imaging (DTI) is underway to provide converging evidence from an anatomical perspective on this issue. •Gamma phase synchrony may be underpinned by the patterns of neurotransmitters including GABA and glutamate.5 Sex differences in the lateralization of these neurotransmitters may also account for the findings of this study.6 •The use of pharmacological probes in future studies will clarify this issue of neuromodulated laterality. References
1. Hiscock M. et al. Is there a sex difference in human laterality? II. An exhaustive survey of visual laterality studies from six neuropsychology journals. J Clin Exp Neuropsychol. 17(4), 590-610 (1995). 2. Basar-Eroglu, C. et al. Gamma-band responses in the brain: a short review of psychophysiological correlates and functional significance. Int J Psychophysio. 24, 101–112 (1996). 3. Haig, A.R. et al. Synchronous cortical gamma-band activity in task-relevant cognition. NeuroReport, 11 (4): 669-675 (2000). 4. Davitzikos, C. & Sresnick, S. Sex differences in anatomic measures of interhemispheric connectivity: Correlation in cognition in women but not men. Cerebral Cortex. 8: 635-640 (1998). 5. Lee KH. et al. Synchronous gamma activity: a review and contribution to an integrative neuroscience model of schizophrenia. Brain Research - Brain Research Reviews. 41 (1):57-78 (2003). 6. Glick, S.D. et al. Lateral asymmetry of neurotransmitters in the human brain. Brain Research. 234 (1): 53-63 (1982).
Methods • Subjects: 550 healthy volunteers from the Brain Resource International Database analyzed in 2 groups: Male (n=275, mean age = 32.7 ± 15.0 yrs) Female (n=275, mean age = 33.2 ± 15.5 yrs) • Psychophysiology: 32 EEG channels (10-20 International system); Gamma phase synchrony obtained from conventional auditory oddball.3 • Analysis: MANCOVA (controlling age and handedness) of frontal versus posterior Gamma synchrony, with sex as between-group factor. MANCOVA (controlling age and handedness) of left frontal versus right frontal Gamma synchrony with sex as between-group factor.
2A (Females)
Time (ms)
2B (Males)
Time (ms)
Upper graphs:
• Females (1A) showed significant synchronisation of early Gamma in the frontal (red) (F1,520= 4.52, p = .03), but not posterior region (blue). • Males (1B) did not show this frontal-posterior gradient.
Lower graphs:
• Males (2B) showed significant desynchronization of late Gamma in the left frontal (black) (F1,500= 9.59, p = .00), but not right frontal region (gray). • Females (2A) did not show this lateralized pattern in the frontal region. • 0ms corresponds to presentation of the target stimulus. • In all graphs: 0ms indicates stimulus onset and dashed gray line indicates prestimulus baseline synchrony.
For further details contact: Rebecca Hamilton: rebecca@brainresource.com