Why sex matters for neuroscience

Key Points

  • This review addresses some of the primary reasons why the sex of participants is an important factor that should be considered in studies at all levels of neuroscience.

  • There are widespread misconceptions about brain sex differences in the field.

  • Sex differences exist in every major part of the brain.

  • New methods are revealing previously unsuspected sex differences.

  • Many regions of the brain that are responsible for cognitive processes, such as the hippocampus, amygdala and neocortex, are sexually dimorphic.

  • A consideration of sex influences can help to reconcile seemingly contradictory findings in neuroscientific research.

  • Active investigation of sex influences is mandatory to fully understand and treat a host of brain disorders with sex differences in the incidence and/or nature.

  • Sex matters for understanding brain function much more than has been widely assumed in neuroscience, and perhaps much more than we yet recognize.

Abstract

A rapidly burgeoning literature documents copious sex influences on brain anatomy, chemistry and function. This article highlights some of the more intriguing recent discoveries and their implications. Consideration of the effects of sex can help to explain seemingly contradictory findings. Research into sex influences is mandatory to fully understand a host of brain disorders with sex differences in their incidence and/or nature. The striking quantity and diversity of sex-related influences on brain function indicate that the still widespread assumption that sex influences are negligible cannot be justified, and probably retards progress in our field.

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Figure 1: An illustration of sex differences in the size of various human brain regions.
Figure 2: Demonstration of oestrus cycle influence on maze learning strategy in rats.
Figure 3: Sex differences in the relationship between amygdala activity during emotional experiences and memory for those experiences.
Figure 4: Rates of serotonin synthesis in men and women.

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Glossary

Voxel-based morphometry

(VBM). A computational approach to neuroanatomy that measures differences in local concentrations of brain tissue through a voxel-wise comparison of multiple brain images. The value of VBM is that it allows for comprehensive measurement of differences, not just in specific structures, but throughout the entire brain.

Long-term potentiation

(LTP). An enduring increase in the amplitude of excitatory postsynaptic potentials as a result of high-frequency (tetanic) stimulation of afferent pathways. It is measured as an increase in the amplitude of excitatory postsynaptic potentials or in the magnitude of the postsynaptic cell population spike. LTP is most frequently studied in the hippocampus and is often considered to be part of the cellular basis of learning and memory in vertebrates.

Fibromyalgia

A chronic, painful condition, primarily occurring in women, characterized by widespread musculoskeletal pain, fatigue and tender points at defined locations.

Fibromyalgia

A chronic, painfull condition, Primarily occurring in women, characterized by widespread musculoskeletal pains, fatigue and tender points at defined locations.

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Cahill, L. Why sex matters for neuroscience. Nat Rev Neurosci 7, 477–484 (2006). https://doi.org/10.1038/nrn1909

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