The Effect of Sex Differences on Brain Stimulation

A recent development in the world of neuroscience has been the rise of a technology called Brain Stimulation. Although some stimulation technologies have existed for a long time (deep brain stimulation to treat Parkinson’s), a recent wave of cheap, available stimulation technologies have provided a myriad of interesting possibilities for treatment of diseases, cognitive enhancement, and human brain research. Brain stimulation has been shown to confer all sorts of effects, from increased motor skill, better memory, stronger visual acuity, better concentration, and many others. Brain stimulation can be accomplished via many methods, including transcranial magnetic stimulation (TMS), transcranial pulsed ultrasonic stimulation (TPU), microelectrode array stimulation and deep brain stimulation. Although these technologies have many benefits (accessibility, academic validity, accuracy), transcranial direct current stimulation (tDCS) is best situated with a balance of price, accuracy, evidence, and accessibility. This has elicited an enormous amount of interest from researchers and the public alike .

tDCS is a technology that uses small amounts of voltage with low direct current to slightly raise the base level of depolarization (anodal stimulation) or hyperpolarization (cathodal stimulation) at the neuronal level of a specific area of cortex. Research seems to suggest that anodal stimulation increases activity, whereas cathode stimulation decreases activity. This could be crucial in replicating or promoting desired brain states, as many brain states rely on deactivation as well as activation. Side effects of the technology depend on the individual and range from small headaches to tingling across the scalp. Because of the mechanisms involved in a neural action potential, raising the level of depolarization, tDCS effectively lowers the threshold needed to fire a neural message. Therefore, any cortical area stimulated with tDCS will see higher rates of activation than normal. It is important to note that tDCS does not elicit activation. Rather, it amplifies the tendencies that already exist within the brain for individual neurons to fire. Other brain stimulation methods such as TMS or TPU induce activation that is not generated via natural depolarization or hyperpolarization, which makes tDCS that much more attractive. Via plasticity mechanisms such as long-term potentiation, tDCS can enhance activation patterns and strengthen neural pathways much faster than normal mechanisms. tDCS has a short-term effect on the brain, and suggest that it achieves its effects through use-dependent synaptic plasticity (Demirtas-Tatlidede, 2013). This ‘amplification’ or ‘depressing’ effect has enormous potential, especially when applied to a training context.

Questions may be raised, however, of the different effects that tDCS may have males and females. There is a large body of literature suggesting that sex differences exist in the brain; it follows that tDCS may have different effects in areas of the brain where sex plays an important role in differentiation. There is evidence to suggest that certain types of stimulation work better in women than in men, specifically in the motor cortex stimulation, a main area of tDCS research and applications. Nitsche et al. state that cathodal stimulation is more effective than anodal stimulation in women, but it is the opposite in men. Anodal stimulation, on the other hand, is more effective in stimulating the visual cortex of brain (Nitsche et al., 2008). Chaieb, Antal, & Paulus, (2008) examined the effectiveness of tDCS in different genders as well; they found that women responded extremely well to anodal stimulation, and its effects persisted at least 10 minutes after stimulation. Conversely, men experienced a dampened activation effect in the same brain area with the same stimulation.

The attached figure from Chaieb et al. shows clear differences between men and women for the persistence of tDCS effects. On the left half of the figure, cathodal stimulation produced similar effects in both the male and female groups; on the right half, a significant difference is shown from 0 minutes after stimulation to 10 minutes after stimulation.

These effects have significant implications for the future of brain stimulation; the results presented in the current studies suggest that women may be more susceptible to brain stimulation. This is most likely caused by increased plasticity in the brain, allowing for the stimulation to take on a greater effect. By maintaining a high level of plasticity and being sensitive to brain changes, women may benefit more from external training and stimulation tools such as tDCS. Men, however, may need additional therapy or stimulation to attain the same effects. Based on the presented works, considerations should be made for different gender groups when conducting experiments with tDCS, and eventual applications of the technology should be aware of its different effects on males and females alike.

References

Chaieb, L., Antal, A., & Paulus, W. (2008). Gender-specific modulation of short-term neuroplasticity in the visual cortex induced by transcranial direct current stimulation. Visual neuroscience, 25(01), 77-81.

Demirtas-Tatlidede, A., Vahabzadeh-Hagh, A. M., & Pascual-Leone, A. (2013). Can noninvasive brain stimulation enhance cognition in neuropsychiatric disorders?. Neuropharmacology, 64, 566-578.

de Tommaso, M., Invitto, S., Ricci, K., Lucchese, V., Delussi, M., Quattromini, P., ... & Cicinelli, E. (2014). Effects of anodal TDCS stimulation of left parietal cortex on visual spatial attention tasks in men and women across menstrual cycle. Neuroscience letters, 574, 21-25.

Fitz, N. S. & Reiner, P. B. (2013). The challenge of crafting policy for do-it-yourself brain stimulation. J Med Ethics. doi:10.1136/medethics-2013-101458

Keshvari, F., Pouretemad, H. R., & Ekhtiari, H. (2013). The effect of gender on dorsolateral prefrontal cortex transcranial DC stimulation-induced disruption of moral judgment. Advances in Cognitive Science, 14(456), 1-12.

Kuo, M. F., Paulus, W., & Nitsche, M. A. (2006). Sex differences in cortical neuroplasticity in humans. Neuroreport, 17(16), 1703-1707.

Lapenta, O. M., Fregni, F., Oberman, L. M., & Boggio, P. S. (2012). Bilateral temporal cortex transcranial direct current stimulation worsens male performance in a multisensory integration task. Neuroscience Letters, 527(2)

Nitsche, M. A., Cohen, L. G., Wassermann, E. M., Priori, A., Lang, N., Antal, A., ... & Pascual-Leone, A. (2008). Transcranial direct current stimulation: state of the art 2008. Brain Stimulation, 1(3), 206-223.