Gender and Brain Stimulation

  • Vanteemar S. Sreeraj
  • Ganesan VenkatasubramanianEmail author
Reference work entry
Part of the Mental Health and Illness Worldwide book series (MHIW)


Neuromodulatory techniques are gaining increasing interest toward application in understanding the pathogenesis as well as therapeutics of several neuropsychiatric disorders. Several factors modulate the effect of these techniques on brain function. Given the significant influence of gender on brain structure and function, it is important to evaluate its potential role in brain stimulation. With this in focus, this chapter summarizes the basic principles of several neuromodulatory techniques as well as the biology of sex differences in the human brain. The potential mechanistic basis through which these biological factors might interact with brain stimulation techniques is reviewed. Contextually, the available literature to support the differential effect of gender on the effect of brain stimulation techniques is summarized.


Gender Brain stimulation Sexual dimorphism TMS tDCS 



This work is supported by the Department of Science and Technology (Government of India) Research Grant to GV (DST/SJF/LSA-02/2014-5).


  1. Adenzato M, Brambilla M, Manenti R, De Lucia L, Trojano L, Garofalo S, Enrici I, Cotelli M (2017) Gender differences in cognitive theory of mind revealed by transcranial direct current stimulation on medial prefrontal cortex. Sci Rep 7:41219. Scholar
  2. Agarwal SM, Shivakumar V, Bose A, Subramaniam A, Nawani H, Chhabra H, Kalmady SV, Narayanaswamy JC, Venkatasubramanian G (2013) Transcranial direct current stimulation in schizophrenia. Clin Psychopharmacol Neurosci Off Sci J Korean Coll Neuropsychopharmacol 11(3):118–125. Scholar
  3. American Psychiatric Association (2008) The practice of electroconvulsive therapy: recommendations for treatment, training, and privileging (A task force report of the American Psychiatric Association). American Psychiatric PublishingGoogle Scholar
  4. Antal A, Paulus W (2013) Transcranial alternating current stimulation (tACS). Front Hum Neurosci 7:317. Scholar
  5. Auyeung B, Knickmeyer R, Ashwin E, Taylor K, Hackett G, Baron-Cohen S (2012) Effects of fetal testosterone on visuospatial ability. Arch Sex Behav 41(3):571–581. Scholar
  6. Barth C, Villringer A, Sacher J (2015) Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods. Front Neurosci 9:37. Scholar
  7. Bianchi MS, Ferreira CF, Fregni F, Schestatsky P, Caumo W, Wender MCO (2017) Transcranial direct current stimulation effects on menopausal vasomotor symptoms. Menopause 24(10):1122–1128. Scholar
  8. Bloch Y, Ratzoni G, Sobol D, Mendlovic S, Gal G, Levkovitz Y (2005) Gender differences in electroconvulsive therapy: a retrospective chart review. J Affect Disord 84(1):99–102. Scholar
  9. Bolu A, Ozselek S, Akarsu S, Alper M, Balikci A (2015) Is there a role of gender in electroconvulsive therapy response? Klinik Psikofarmakoloji Bul-Bull Clin Psychopharmacol 25(3):228–232. Scholar
  10. Chahine G, Short B, Spicer K, Schmidt M, Burns C, Atoui M, George MS, Sackeim HA, Nahas Z (2014) Regional cerebral blood flow changes associated with focal electrically administered seizure therapy (FEAST). Brain Stimul 7(3):483–485. Scholar
  11. Chaieb L, Antal A, Paulus W (2008) Gender-specific modulation of short-term neuroplasticity in the visual cortex induced by transcranial direct current stimulation. Vis Neurosci 25(1):77–81. Scholar
  12. Chandran S, Krishnan S, Rao RM, Sarma SG, Sarma PS, Kishore A (2014) Gender influence on selection and outcome of deep brain stimulation for Parkinson’s disease. Ann Indian Acad Neurol 17(1):66–70. Scholar
  13. Cretaz E, Brunoni AR, Lafer B (2015) Magnetic seizure therapy for unipolar and bipolar depression: a systematic review. Neural Plast 2015:521398. Scholar
  14. D’Urso G, Dell’Osso B, Rossi R, Brunoni AR, Bortolomasi M, Ferrucci R, Priori A, de Bartolomeis A, Altamura AC (2017) Clinical predictors of acute response to transcranial direct current stimulation (tDCS) in major depression. J Affect Disord 219:25–30. Scholar
  15. Else-Quest NM, Hyde JS, Goldsmith HH, Van Hulle CA (2006) Gender differences in temperament: a meta-analysis. Psychol Bull 132(1):33–72. Scholar
  16. Figee M, Bervoets C, Denys D (2017) Deep brain stimulation in psychiatry. Tijdschr Psychiatr 59(10):638–642PubMedGoogle Scholar
  17. Filmer HL, Dux PE, Mattingley JB (2014) Applications of transcranial direct current stimulation for understanding brain function. Trends Neurosci 37(12):742–753. Scholar
  18. Fumagalli M, Vergari M, Pasqualetti P, Marceglia S, Mameli F, Ferrucci R, Mrakic-Sposta S, Zago S, Sartori G, Pravettoni G, Barbieri S, Cappa S, Priori A (2010) Brain switches utilitarian behavior: does gender make the difference? PLoS One 5(1):e8865. Scholar
  19. Geduldig ET, Kellner CH (2016) Electroconvulsive therapy in the elderly: new findings in geriatric depression. Curr Psychiatry Rep 18(4):40. Scholar
  20. Goldstein JM, Holsen L, Handa R, Tobet S (2014) Fetal hormonal programming of sex differences in depression: linking women’s mental health with sex differences in the brain across the lifespan. Front Neurosci 8:247. Scholar
  21. Guleyupoglu B, Schestatsky P, Edwards D, Fregni F, Bikson M (2013) Classification of methods in transcranial electrical stimulation (tES) and evolving strategy from historical approaches to contemporary innovations. J Neurosci Methods 219(2):297–311. Scholar
  22. Hanamsagar R, Bilbo SD (2016) Sex differences in neurodevelopmental and neurodegenerative disorders: focus on microglial function and neuroinflammation during development. J Steroid Biochem Mol Biol 160:127–133. Scholar
  23. Haraguchi S, Sasahara K, Shikimi H, Honda S, Harada N, Tsutsui K (2012) Estradiol promotes purkinje dendritic growth, spinogenesis, and synaptogenesis during neonatal life by inducing the expression of BDNF. Cerebellum 11(2):416–417. Scholar
  24. Hill AC, Laird AR, Robinson JL (2014) Gender differences in working memory networks: a BrainMap meta-analysis. Biol Psychol 102:18–29. Scholar
  25. Hyde JS (2016) Sex and cognition: gender and cognitive functions. Curr Opin Neurobiol 38:53–56. Scholar
  26. Inghilleri M, Conte A, Curra A, Frasca V, Lorenzano C, Berardelli A (2004) Ovarian hormones and cortical excitability. An rTMS study in humans. Clin Neurophysiol Off J Int Fed Clin Neurophysiol 115(5):1063–1068. Scholar
  27. Joel D, Berman Z, Tavor I, Wexler N, Gaber O, Stein Y, Shefi N, Pool J, Urchs S, Margulies DS, Liem F, Hanggi J, Jancke L, Assaf Y (2015) Sex beyond the genitalia: the human brain mosaic. Proc Natl Acad Sci U S A 112(50):15468–15473. Scholar
  28. Kuo MF, Paulus W, Nitsche MA (2006) Sex differences in cortical neuroplasticity in humans. Neuroreport 17(16):1703–1707. Scholar
  29. Kurzeck A, Kirsch B, Weidinger E, Padberg F, Palm U (2018) Transcranial Direct Current Stimulation (tDCS) for depression during pregnancy: scientific evidence and what is being said in the media-a systematic review. Brain Sci 8(8):155.
  30. Lee S, Chung SW, Rogasch NC, Thomson CJ, Worsley RN, Kulkarni J, Thomson RH, Fitzgerald PB, Segrave RA (2018) The influence of endogenous estrogen on transcranial direct current stimulation: a preliminary study. Eur J Neurosci 48(4):2001–2012. Scholar
  31. Leiknes KA, Jarosh-von Schweder L, Hoie B (2012) Contemporary use and practice of electroconvulsive therapy worldwide. Brain Behavior 2(3):283–344. Scholar
  32. Lisanby SH (2004) Brain stimulation in psychiatric treatment. American Psychiatric Publishing, Washington, DCGoogle Scholar
  33. Loo CK, Katalinic N, Martin D, Schweitzer I (2012) A review of ultrabrief pulse width electroconvulsive therapy. Ther Adv Chronic Dis 3(2):69–85. Scholar
  34. Malik AM, Haque Z, Ide G, Farley A (2016) Gender and age as factors in response and remission of depression treated with transcranial magnetic stimulation. Brain Stimul Basic Transl Clin Res Neuromodulation 9(5):e7. Scholar
  35. Manohar H, Subramanian K, Menon V, Kattimani S (2017) Does gender influence electroconvulsive therapy sessions required across psychiatric diagnoses? A 5-year experience from a single center. J Neurosci Rural Pract 8(3):427–430. Scholar
  36. Martin AK, Huang J, Hunold A, Meinzer M (2017) Sex mediates the effects of high-definition transcranial direct current stimulation on “mind-reading”. Neuroscience 366:84–94. Scholar
  37. McCall WV, Andrade C, Sienaert P (2014) Searching for the mechanism(s) of ECT’s therapeutic effect. J ECT 30(2):87–89. Scholar
  38. McCarthy MM (2016) Sex differences in the developing brain as a source of inherent risk. Dialogues Clin Neurosci 18(4):361–372PubMedPubMedCentralGoogle Scholar
  39. Meiron O, Lavidor M (2013) Unilateral prefrontal direct current stimulation effects are modulated by working memory load and gender. Brain Stimul 6(3):440–447. Scholar
  40. Miller DI, Halpern DF (2014) The new science of cognitive sex differences. Trends Cogn Sci 18(1):37–45. Scholar
  41. Miniussi C, Paulus W, Rossini PM (2013) Transcranial brain stimulation. Frontiers in neuroscience. Taylor & Francis, Boca RatonGoogle Scholar
  42. Mishra BR, Sarkar S, Praharaj SK, Mehta VS, Diwedi S, Nizamie SH (2011) Repetitive transcranial magnetic stimulation in psychiatry. Ann Indian Acad Neurol 14(4):245–251. Scholar
  43. Muller HHO, Moeller S, Lucke C, Lam AP, Braun N, Philipsen A (2018) Vagus Nerve Stimulation (VNS) and other augmentation strategies for Therapy-Resistant Depression (TRD): review of the evidence and clinical advice for use. Front Neurosci 12:239. Scholar
  44. Mylius V, Ayache SS, Ahdab R, Farhat WH, Zouari HG, Belke M, Brugieres P, Wehrmann E, Krakow K, Timmesfeld N, Schmidt S, Oertel WH, Knake S, Lefaucheur JP (2013) Definition of DLPFC and M1 according to anatomical landmarks for navigated brain stimulation: inter-rater reliability, accuracy, and influence of gender and age. NeuroImage 78:224–232. Scholar
  45. Nahas Z, Short B, Burns C, Archer M, Schmidt M, Prudic J, Nobler MS, Devanand DP, Fitzsimons L, Lisanby SH, Payne N, Perera T, George MS, Sackeim HA (2013) A feasibility study of a new method for electrically producing seizures in man: focal electrically administered seizure therapy [FEAST]. Brain Stimul 6(3):403–408. Scholar
  46. Pellegrini M, Zoghi M, Jaberzadeh S (2018) Biological and anatomical factors influencing interindividual variability to noninvasive brain stimulation of the primary motor cortex: a systematic review and meta-analysis. Rev Neurosci 29(2):199–222. Scholar
  47. Peterchev AV, Rosa MA, Deng ZD, Prudic J, Lisanby SH (2010) Electroconvulsive therapy stimulus parameters: rethinking dosage. J ECT 26(3):159–174. Scholar
  48. Phoenix CH, Goy RW, Gerall AA, Young WC (1959) Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology 65:369–382. Scholar
  49. Pinot-Monange A, Moisset X, Chauvet P, Gremeau AS, Comptour A, Canis M, Pereira B, Bourdel N (2019) Repetitive Transcranial Magnetic Stimulation Therapy (rTMS) for endometriosis patients with refractory pelvic chronic pain: a pilot study. J Clin Med 8(4):508.
  50. Pletzer B (2015) Editorial: from sex differences in neuroscience to a neuroscience of sex differences: new directions and perspectives. Front Neurosci 9:330. Scholar
  51. Pletzer BA, Kerschbaum HH (2014) 50 years of hormonal contraception-time to find out, what it does to our brain. Front Neurosci 8:256. Scholar
  52. Pompili M, Dominici G, Giordano G, Longo L, Serafini G, Lester D, Amore M, Girardi P (2014) Electroconvulsive treatment during pregnancy: a systematic review. Expert Rev Neurother 14(12):1377–1390. Scholar
  53. Prehn-Kristensen A, Munz M, Goder R, Wilhelm I, Korr K, Vahl W, Wiesner CD, Baving L (2014) Transcranial oscillatory direct current stimulation during sleep improves declarative memory consolidation in children with attention-deficit/hyperactivity disorder to a level comparable to healthy controls. Brain Stimul 7(6):793–799. Scholar
  54. Ridding MC, Ziemann U (2010) Determinants of the induction of cortical plasticity by non-invasive brain stimulation in healthy subjects. J Physiol 588(Pt 13):2291–2304. Scholar
  55. Rostami R, Badran BW, Kazemi R, Habibnezhad M, George MS (2015) Long-lasting analgesic effect of transcranial direct current stimulation in treatment of chronic endometriosis pain. J Obstet Gynaecol Res 41(12):1998–2001. Scholar
  56. Rubens MT, Zanto TP (2012) Parameterization of transcranial magnetic stimulation. J Neurophysiol 107(5):1257–1259. Scholar
  57. Ruigrok AN, Salimi-Khorshidi G, Lai MC, Baron-Cohen S, Lombardo MV, Tait RJ, Suckling J (2014) A meta-analysis of sex differences in human brain structure. Neurosci Biobehav Rev 39:34–50. Scholar
  58. Russell M, Goodman T, Wang Q, Groshong B, Lyeth BG (2014) Gender differences in current received during transcranial electrical Stimulation. Front Psychol 5:104. Scholar
  59. Sackeim H, Decina P, Prohovnik I, Malitz S (1987) Seizure threshold in electroconvulsive therapy. Effects of sex, age, electrode placement, and number of treatments. Arch Gen Psychiatry 44(4):355–360CrossRefGoogle Scholar
  60. Sackeim HA, Prudic J, Fuller R, Keilp J, Lavori PW, Olfson M (2007) The cognitive effects of electroconvulsive therapy in community settings. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 32(1):244–254. Scholar
  61. Savic I (2014) Asymmetry of cerebral gray and white matter and structural volumes in relation to sex hormones and chromosomes. Front Neurosci 8:329. Scholar
  62. Shenoy S, Bose A, Chhabra H, Dinakaran D, Agarwal SM, Shivakumar V, Narayanaswamy JC, Sivakumar PT, Venkatasubramanian G (2015) Transcranial direct current stimulation (tDCS) for auditory verbal hallucinations in schizophrenia during pregnancy: a case report. Brain Stimul 8(1):163–164. Scholar
  63. Sienaert PA, Geeraerts I (2013) Menstrual disturbances during electroconvulsive therapy: the forgotten adverse effect: case report and review of the literature. J ECT 29(1):58–60. Scholar
  64. Smith MJ, Keel JC, Greenberg BD, Adams LF, Schmidt PJ, Rubinow DA, Wassermann EM (1999) Menstrual cycle effects on cortical excitability. Neurology 53(9):2069–2072CrossRefGoogle Scholar
  65. Smith MD, Jones LS, Wilson MA (2002) Sex differences in hippocampal slice excitability: role of testosterone. Neuroscience 109(3):517–530CrossRefGoogle Scholar
  66. Sreeraj VS, Bose A, Shanbhag V, Narayanaswamy JC, Venkatasubramanian G, Benegal V (2016) Monotherapy with tDCS for treatment of depressive episode during pregnancy: a case report. Brain Stimul 9(3):457–458. Scholar
  67. Sreeraj VS, Shivakumar V, Sowmya S, Bose A, Nawani H, Narayanaswamy JC, Venkatasubramanian G (2019) Online theta frequency transcranial alternating current stimulation for cognitive remediation in schizophrenia: a case report and review of literature. J ECT 35(2):139–143. Scholar
  68. Stimulation B (2018) Brain stimulation (Journal Online) basic, translational, and clinical research in neuromodulation. Elsevier B V. Accessed 10 May 2018
  69. Su R, Rounds J, Armstrong PI (2009) Men and things, women and people: a meta-analysis of sex differences in interests. Psychol Bull 135(6):859–884. Scholar
  70. Szalkai B, Varga B, Grolmusz V (2015) Graph theoretical analysis reveals: women’s brains are better connected than men’s. PLoS One 10(7):e0130045. Scholar
  71. Vasudevan N, Pfaff DW (2008) Non-genomic actions of estrogens and their interaction with genomic actions in the brain. Front Neuroendocrinol 29(2):238–257. Scholar
  72. Vigod S, Dennis CL, Daskalakis Z, Murphy K, Ray J, Oberlander T, Somerton S, Hussain-Shamsy N, Blumberger D (2014) Transcranial direct current stimulation (tDCS) for treatment of major depression during pregnancy: study protocol for a pilot randomized controlled trial. Trials 15:366. Scholar
  73. Yu H, Neimat JS (2008) The treatment of movement disorders by deep brain stimulation. Neurother J Am Soc Exp Neurother 5(1):26–36. Scholar
  74. Zell E, Krizan Z, Teeter SR (2015) Evaluating gender similarities and differences using metasynthesis. Am Psychol 70(1):10–20. Scholar
  75. Zoghi M, Vaseghi B, Bastani A, Jaberzadeh S, Galea MP (2015) The effects of sex hormonal fluctuations during menstrual cycle on cortical excitability and manual dexterity (a pilot study). PLoS One 10(8):e0136081. Scholar

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© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  • Vanteemar S. Sreeraj
    • 1
  • Ganesan Venkatasubramanian
    • 1
    Email author
  1. 1.WISER Neuromodulation Program, Department of PsychiatryNational Institute of Mental Health and Neurosciences (NIMHANS)BengaluruIndia

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