Sex difference in tDCS current mediated by changes in cortical anatomy: a study across young, middle and older adults
Open accessAbstract
INTRODUCTION: The observed variability in the effects of transcranial direct current stimulation (tDCS) is influenced by the amount of current reaching the targeted region-of-interest (ROI). Age and sex might affect current density at target ROI due to their impact on cortical anatomy. The present tDCS simulation study investigates the effects of cortical anatomical parameters (volumes, dimension, and torque) on simulated tDCS current density in healthy young, middle-aged, and older males and females. METHODOLOGY: electrode) from two simulated tDCS montages (CP5_CZ and F3_FP2) targeting the inferior parietal lobule (IPL) and middle frontal gyrus (MFG), respectively. Cortical parameters including segmented brain volumes (cerebrospinal fluid [CSF], grey and white matter), cerebral-dimensions (length/width &length/height) and brain-torque (front and back shift, petalia, and bending) were measured using the magnetic resonance images (MRIs) from each subject. The present study estimated sex differences in current density at these target ROIs mediated by these cortical parameters within each age group. RESULTS: For both tDCS montages, females in the older age group received higher current density than their male counterparts at the target ROIs. No sex differences were observed in the middle-aged group. Males in the younger age group had a higher current density than females, only for the parietal montage. Across all age groups, CSF, and grey matter volumes significantly predicted the current intensity estimated at the target sites. In the older age group only, brain-torque was a significant mediator of the sex difference. CONCLUSIONS: Our findings demonstrate the presence of sex differences in the simulated tDCS current density, however this pattern differed across age groups and stimulation locations. Future studies should consider influence of age and sex on individual cortical anatomy and tailor tDCS stimulation parameters accordingly.
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Female older adults receive higher current density in targeted regions than their male counterparts, mediated by sex differences in brain structure.
“Mediated by sex differences in brain structure, female older adults receive higher current density in targeted regions than their male counterparts [64], which may partly explain these discrepancies given the male-dominated active stimulation group in phase 1.”
From Primary outcome from the augmenting cognitive training in older adults study (ACT): A tDCS and cognitive training randomized clinical trial (2023) · cites this paper as [64]
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Li, X., Crow, T. J., & Roberts, N. (2019) · Brain Structure and Function · doi:10.1007/s00429-018-01818-0 · Cited by 44 · cited 3× · see citing works
“the specific right-frontal and left-occipital protrusion is present in 60% of the human population [37].”
BackgroundThe influence of endogenous estrogen on transcranial direct current stimulation: A preliminary study
Lee, S., Chung, S. W., Rogasch, N. C., Thomson, C. J., Worsley, R., Kulkarni, J., Thomson, R. H., Fitzgerald, P. B., & Segrave, R. A. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14085 · Cited by 41 · cited 1× · see citing works
“10 Lee et al, 2018 [64] 15 M, 14 F F = 22.”
León, J. J., Sánchez-Kuhn, A., Fernández‐Martín, P., Páez-Pérez, M. A., Thomas, C., Datta, A., Sánchez-Santed, F., & Flores, P. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112485 · Cited by 40 · see citing works
Baharlouei, H., Saba, M. A., Yazdi, M. J. S., & Jaberzadeh, S. J. (2020) · Neurophysiologie Clinique · doi:10.1016/j.neucli.2020.01.006 · Cited by 39 · see citing works
Lapenta, O. M., Fregni, F., Oberman, L. M., & Boggio, P. S. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.08.076 · Cited by 39 · see citing works
Human torque is not present in chimpanzee brain
Li, X., Crow, T. J., Hopkins, W. D., Gong, Q., & Roberts, N. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.10.017 · Cited by 37 · cited 1× · see citing works
“It refers to an anticlockwise twist of the brain around the ventral-dorsal axis [37,38].”
Workman, C. D., Kamholz, J. A., & Rudroff, T. (2019) · Brain Sciences · doi:10.3390/brainsci10010012 · Cited by 37 · cited 2× · see citing works
“However, more investigations are required regarding the safety and tolerability of participants in using such high current intensities [72].”
Thomas, C., Ghodratitoostani, I., Delbem, A. C. B., Ali, A., & Datta, A. (2019) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/embc.2019.8856898 · Cited by 37 · cited 2× · see citing works
“To support the sex difference in tDCS outcomes, only one simulation study with MRI images of 5 males and 5 females (spanning ages 27e47 years) reported females having higher current density at the motor cortex than males [23].”
Schulte-Geers, C., Obert, M., Schilling, R. L., Harth, S., Traupe, H., Gizewski, E. R., & Verhoff, M. A. (2011) · International Journal of Legal Medicine · doi:10.1007/s00414-010-0544-3 · Cited by 37 · cited 1× · see citing works
“29 which could, in turn, vary between males and females [95].”
BackgroundTranscranial direct current stimulation over prefrontal cortex diminishes degree of risk aversion
Ye, H., Chen, S., Huang, D., Wang, S., Jia, Y., & Luo, J. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2015.04.050 · Cited by 32 · see citing works
Self-citationAging, sex and cognitive Theory of Mind: a transcranial direct current stimulation study
Adenzato, M., Manenti, R., Gobbi, E., Enrici, I., Rusich, D., & Cotelli, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-54469-4 · Cited by 31 · cited 1× · see citing works
“5mA 30 min on 2 days per week for 3weeks Female patients showed superior treatment response in contrast to male patients Adenzato et al 2019[22] 15M and 15F per anodal and cathodal group 67.”
Rezaee, Z., & Dutta, A. (2020) · Neuromodulation Technology at the Neural Interface · doi:10.1111/ner.13098 · Cited by 27 · see citing works
Thomas, C., Datta, A., & Woods, A. J. (2018) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/embc.2018.8513014 · Cited by 26 · cited 1× · see citing works
“Prior research studies suggest that simulated current density at a target ROI decreases with increasing age [9,16,17].”
Unal, G., Ficek, B., Webster, K. T., Shahabuddin, S., Truong, D. Q., Hampstead, B. M., Bikson, M., & Tsapkini, K. (2020) · Neurological Sciences · doi:10.1007/s10072-019-04229-z · Cited by 26 · see citing works
Simulation Analyses of tDCS Montages for the Investigation of Dorsal and Ventral Pathways
Bhattacharjee, S., Kashyap, R., Rapp, B. C., Oishi, K., Desmond, J. E., & Chen, S. A. (2019) · Scientific Reports · doi:10.1038/s41598-019-47654-y · Cited by 26 · cited 15× · see citing works
“Two montages CP5_CZ and F3_FP2 were simulated targeting two ROIs left inferior parietal lobule (IPL) and left middle frontal gyrus (MFG), respectively.”
InfluentialSelf-citationSingle-Layer Skull Approximations Perform Well in Transcranial Direct Current Stimulation Modeling
Rampersad, S. M., Stegeman, D. F., & Oostendorp, T. F. (2012) · IEEE Transactions on Neural Systems and Rehabilitation Engineering · doi:10.1109/tnsre.2012.2206829 · Cited by 25 · cited 1× · see citing works
“The porous nature of the male skull might have contributed to this finding as studies have reported that single layer approximation and three-layered skull modelling don't produce much difference in the final simulated current [86,87], although the opposite view also exists [88].”
Workman, C. D., Fietsam, A. C., & Rudroff, T. (2020) · Brain Sciences · doi:10.3390/brainsci10040244 · Cited by 25 · cited 1× · see citing works
“8 Workman et al 2020 [54] 10M, 10 F Mean age 24.”
Fehring, D. J., Samandra, R., Haque, Z. Z., Jaberzadeh, S., Rosa, M. G. P., & Mansouri, F. A. (2021) · Biology of Sex Differences · doi:10.1186/s13293-021-00390-3 · Cited by 23 · cited 1× · see citing works
“, 2021 [59] 37 females, 36 males 18–32 years old Practice-related learning in the Stop-Signal Task Anode = 2.”
Backgroundde Tommaso, M., Invitto, S., Ricci, K., Lucchese, V., Delussi, M. D., Quattromini, P., Bettocchi, S., Pinto, V., Lancioni, G. E., Livrea, P., et al. (2014) · Neuroscience Letters · doi:10.1016/j.neulet.2014.05.014 · Cited by 23 · see citing works
Gao, M., Yang, X., Shi, J., Lin, Y., & Chen, S. (2018) · Frontiers in Psychology · doi:10.3389/fpsyg.2018.01321 · Cited by 21 · cited 1× · see citing works
“2018 [49] 44 M, 46F Not provided Deception task 5 7 cm2 Anode 1⁄4 F3 Cathode 1⁄4 F4 DLPFC 2 mA 20min”
Self-citationWang, S., Wang, J., Guo, W., Ye, H., Lu, X., Luo, J., & Zheng, H. (2019) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2019.00403 · Cited by 20 · see citing works
Focality-Oriented Selection of Current Dose for Transcranial Direct Current Stimulation
Kashyap, R., Bhattacharjee, S., Arumugam, R., Bharath, R. D., Udupa, K., Oishi, K., Desmond, J. E., Chen, S. A., & Guan, C. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11090940 · Cited by 19 · see citing works
Self-citationImaging Transcranial Direct Current Stimulation (tDCS) with Positron Emission Tomography (PET)
Rudroff, T., Workman, C. D., Fietsam, A. C., & Ponto, L. B. (2020) · Brain Science · doi:10.3390/brainsci10040236 · Cited by 19 · cited 1× · see citing works
“However, future studies with neuroimaging methods like PET, cerebral blood flow and electrophysiological techniques could complement the tDCS modelling studies to clarify the associated physiological changes (for details [98,99]).”
Effect of Modulating Activity of DLPFC and Gender on Search Behavior: A tDCS Experiment
Yang, X., Lin, Y., Gao, M., & Jin, X. (2018) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2018.00325 · Cited by 17 · see citing works
Bhattacharjee, S., Kashyap, R., O'BRIEN, B. A., McCloskey, M. E., Oishi, K., Desmond, J. E., Rapp, B. C., & Chen, S. A. (2020) · Brain and Language · doi:10.1016/j.bandl.2020.104850 · Cited by 15 · cited 1× · see citing works
“The effects of tDCS on response execution (percentage of correct responses) were higher for males but lower for females Bhattacharjee et al 2019, 2020 [60,61] 8M, 6 F F= M= Reading task 5×5 cm(2) Anode = CP5 Anode = TP7 Cathode= Cz Left IPL and left MTG 2mA 20 min”
BackgroundSelf-citationWorkman, C. D., Fietsam, A. C., Kamholz, J. A., & Rudroff, T. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.15070 · Cited by 14 · cited 1× · see citing works
“Interestingly, studies have also shown that higher doses up to 4 mA could be safely used [72] but less tolerable in females compared to males [91].”
Kashyap, R., Bhattacharjee, S., Arumugam, R., Oishi, K., Desmond, J. E., & Chen, S. A. (2020) · Journal of Neural Engineering · doi:10.1088/1741-2552/aba6dc · Cited by 12 · cited 2× · see citing works
“ROAST outputs from each brain were post-processed to estimate current density at the two targets ROIs: left IPL and left MFG using a toolbox Individual-Systematic Approach for tDCS Analysis (i-SATA) developed in our previous work [66].”
BackgroundMethodSelf-citationCould tDCS Modulate Bilingual Reading?
Bhattacharjee, S., Chew, A., Kashyap, R., Wu, C., Yeo, M. M., O'BRIEN, B. A., Rapp, B. C., McCloskey, M. E., Oishi, K., Desmond, J. E., et al. (2019) · Brain stimulation · doi:10.1016/j.brs.2018.12.885 · Cited by 12 · see citing works
Self-citationCotelli, M., Manenti, R., Gobbi, E., Enrici, I., Rusich, D., Ferrari, C., & Adenzato, M. (2020) · Brain Sciences · doi:10.3390/brainsci10050257 · Cited by 11 · cited 1× · see citing works
“In an attempt to investigate the cumulative effect of age and sex, one study [20] combined the data from two separate experiments conducted on young (mean age 23 years) [21] and healthy adults (mean age 67.”
Kashyap, R., Bhattacharjee, S., Sommer, W., & Zhou, C. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14303 · Cited by 8 · cited 1× · see citing works
“However, future studies with neuroimaging methods like PET, cerebral blood flow and electrophysiological techniques could complement the tDCS modelling studies to clarify the associated physiological changes (for details [98,99]).”
Self-citationOn handling the layered structure of the skull in transcranial direct current stimulation models
Rampersad, S. M., Stegeman, D. F., & Oostendorp, T. F. (2011) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/iembs.2011.6090560 · Cited by 7 · cited 4× · see citing works
“As a result, a higher simulated tDCS current density was found for males compared to females (skull modelled as three-layers of compact and spongiform layers), and the difference was more significant at the C3 (near temporoparietal) region compared to F3 (frontal) [86].”
BackgroundInfluential
Flagged first, then by citations
2 of the 108 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- [12]Kim J-H, Kim D-W, Chang WH, Kim Y-H, Kim K, Im C-H. Inconsistent outcomes of transcranial direct current stimulation may originate from anatomical differences among individuals: electric field simulation using individual MRI data. Neuroscience Letters 2014; 564: 6– 10. 24508704
- [88]Sun W, Wang H, Zhang J, Yan T, Pei G. Multi-layer skull modeling and importance for tDCS simulation. Proceedings of the 2021 International Conference on Bioinformatics and Intelligent Computing, 2021, p. 250– 6.
- [100]Russell M, Goodman T, Wang Q, Groshong B, Lyeth BG. Gender differences in current received during transcranial electrical stimulation. Frontiers in Psychiatry 2014; 5: 104. 25177301 PMC4133690
Cited by
Sorted by citations
Vergallito, A., Feroldi, S., Pisoni, A., & Lauro, L. J. R. (2022) · Brain Sciences · doi:10.3390/brainsci12050522 · Cited by 186 · see citing works
“Overlapping results have been reported by Bhattacharjee and colleagues [92] that simulated tDCS induced electrical fields on 240 individual MRIs representative of three age groups (young, middle age, and older adults).”
Gottfried Schlaug, A., Cassarly, C. N., Feld, J., Wolf, S. L., Rowe, V. T., Fritz, S. L., Chhatbar, P. Y., Shinde, A., Su, Z., Broderick, J. P., et al. (2025) · The Lancet Neurology · doi:10.1016/s1474-4422(25)00044-4 · Cited by 50 · see citing works
Licata, A. E., Zhao, Y., Herrmann, O., Hillis, A. E., Desmond, J. E., Onyike, C. U., & Tsapkini, K. (2022) · NeuroImage Clinical · doi:10.1016/j.nicl.2023.103329 · Cited by 26 · see citing works
Self-citationMa, W., Wang, F., Yi, Y., Huang, Y., Li, X., Liu, Y., & Tu, Y. (2024) · 中国科学通报：英文版 · doi:10.1016/j.scib.2024.10.001 · Cited by 24 · see citing works
Koo, G. K., Gaur, A., Tumati, S., Kusumo, R. W., Bawa, K. K., Herrmann, N., Gallagher, D., & Lanctôt, K. L. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105047 · Cited by 25 · see citing works
Spaced Transcranial Direct Current Stimulation for Major Depression
Couture, M., Jodoin, V. D., Bousseau, E., Sarshoghi, A., Nitsche, M. A., Blumberger, D. M., Bolduc, C., Weissman, C. R., Appelbaum, L. G., Daskalakis, Z. J., et al. (2025) · American Journal of Psychiatry · doi:10.1176/appi.ajp.20240083 · Cited by 20 · see citing works
Weller, S., Derntl, B., & Plewnia, C. (2023) · Biology of Sex Differences · doi:10.1186/s13293-023-00561-4 · Cited by 17 · see citing works
“A recent study in a large sample of 240 subjects has shown the extent to which anatomical parameters of the cortex affect the electrical current distribution caused by tDCS [13].”
BackgroundGomez-Tames, J. D., & Fernández-Corazza, M. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13113084 · Cited by 15 · see citing works
“No relationship was found with the sham condition [109].”
BackgroundHausman, H. K., Alexander, G. E., Cohen, R., Marsiske, M., DeKosky, S. T., Hishaw, G. A., O'Shea, A., Kraft, J. N., Dai, Y., Wu, S., et al. (2023) · Brain Stimulation · doi:10.1016/j.brs.2023.05.021 · Cited by 13 · see citing works
“Mediated by sex differences in brain structure, female older adults receive higher current density in targeted regions than their male counterparts [64], which may partly explain these discrepancies given the maledominated active stimulation group in phase 1.”
Fromm, A. E., Trujillo, C., Grittner, U., Meinzer, M., Flöel, A., & Antonenko, D. (2025) · Brain stimulation · doi:10.1016/j.brs.2025.06.005 · Cited by 13 · see citing works
“For example, increased cerebrospinal fluid (CSF) volume disperses current away from the cortex, reducing field intensity at the target site [36,69,73] and also creates more diffuse and inconsistent field patterns in older adults [36, 69].”
Krebs, C. R., Peter, J., Brill, E., Klöppel, S., & Brem, A. (2023) · Frontiers in Psychology · doi:10.3389/fpsyg.2023.1243099 · Cited by 13 · see citing works
“Notably, age-related brain changes differ between females and males, pointing out sex as another factor moderating brain stimulation outcomes (Bhattacharjee et al., 2022).”
BackgroundVural, G., Soldini, A., Padberg, F., Karslı, B., Zinchenko, A., Goerigk, S. A., Soutschek, A., Mezger, E., Stoecklein, S., Bulubas, L., et al. (2024) · Human Brain Mapping · doi:10.1002/hbm.70097 · Cited by 13 · see citing works
Klees‐Themens, G., & Théoret, H. (2023) · European Journal of Neuroscience · doi:10.1111/ejn.16073 · Cited by 12 · see citing works
“…as measured by TMS (Fujiyama et al., 2014; Ghasemian-Shirvan et al., 2020; Heise et al., 2014), gender could impact aftereffects (Kuo et al., 2006) and the interaction between age and gender on individual cortical anatomy could potentially further mediate tDCS response (Bhattacharjee et al., 2022).”
BackgroundThe Effects of Transcranial Direct Current Stimulation in Patients with Mild Cognitive Impairment
Palimariciuc, M., Oprea, D. C., Cristofor, A. C., Florea, T., Dobrin, R., Dobrin, I., Gireadă, B., Gavril, R. S., Mawas, I., Bejenariu, A. C., et al. (2023) · Neurology International · doi:10.3390/neurolint15040092 · Cited by 12 · see citing works
“Understanding these differences is essential for optimizing tDCS applications and tailoring treatments to individuals [35].”
BackgroundKashyap, R., Bhattacharjee, S., Bharath, R. D., Venkatasubramanian, G., Udupa, K., Bashir, S., Oishi, K., Desmond, J. E., Chen, S. A., & Guan, C. (2022) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2022.952602 · Cited by 12 · see citing works
“An interesting point observed in all these studies (Antonenko et al., 2019; Indahlastari et al., 2020; Kashyap et al., 2021; Bhattacharjee et al., 2022) is that population sample is subdivided into groups based on age and sex, and simulations are titrated by changing the tDCS parameters (montage position and current d…”
MethodSelf-citationSwissa, Y., Hacohen, S., Friedman, J., & Frenkel‐Toledo, S. (2022) · Scientific Reports · doi:10.1038/s41598-022-15226-2 · Cited by 11 · see citing works
Applications of open-source software ROAST in clinical studies: A review
Nasimova, M., & Huang, Y. (2022) · Brain stimulation · doi:10.1016/j.brs.2022.07.003 · Cited by 11 · see citing works
“Another relatively large study [48] leveraged ROAST to model N = 240 individuals to study the effects of cortical anatomical parameters such as volumes, dimension, and torque on simulated TES current density in healthy young, middle-aged, and older males and females.”
BackgroundKamii, Y., Kojima, S., & Onishi, H. (2022) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2022.876083 · Cited by 10 · see citing works
“Previous studies have showed differing results of electric field simulation (Kuo et al., 2006; Bhattacharjee et al., 2022) and the effect of tDCS (Thomas et al.”
ResultBattisti, A., Lazzaro, G., Ursumando, L., D’Aiello, B., Zanna, V., Costanzo, F., Vicari, S., & Menghini, D. (2025) · Scientific Reports · doi:10.1038/s41598-025-88256-1 · Cited by 9 · see citing works
“Indeed, previous studies have shown that differences in experimental methods can influence perceptibility and aspects related to the safety and tolerability of tES 38,50–54 .”
Ciricugno, A., Arioli, M., Oldrati, V., Finisguerra, A., Urgesi, C., Borgatti, R., & Cattaneo, Z. (2025) · NeuroImage · doi:10.1016/j.neuroimage.2025.121350 · Cited by 9 · see citing works
Deters, J. R., Fietsam, A. C., Workman, C. D., & Rudroff, T. (2022) · Brain Sciences · doi:10.3390/brainsci12040506 · Cited by 8 · see citing works
“Specifically, modeling studies have reported that sex-specific differences in skull characteristics, which are different between women and men, modulate the amount of current that reaches the cortex [21,22].”
BackgroundKang, D. W., Wang, S., Um, Y. H., Kim, S., Kim, T., Kim, D., Lee, C. U., & Lim, H. K. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1428535 · Cited by 8 · see citing works
Yatsuda, K., Fernández-Corazza, M., Yu, W., & Gomez-Tames, J. D. (2025) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2025.110223 · Cited by 8 · see citing works
Sharpe, B., Sharpe, A., Poulus, D., Obine, E., King, R., Birch, P. D., & Gladwin, T. (2025) · Anxiety, Stress, & Coping · doi:10.1080/10615806.2025.2502792 · Cited by 9 · see citing works
“The exclusive focus on male participants was driven by known structural and functional differences in male and female brain responses to interventions such as transcranial direct current stimulation (see Bhattacharjee et al., 2022; Weller et al., 2023).”
Computation of group-level electric field in lower limb motor area for different tDCS montages
Hamajima, H., Gomez-Tames, J. D., Uehara, S., Otaka, Y., Tanaka, S., & Hirata, A. (2023) · Clinical Neurophysiology · doi:10.1016/j.clinph.2023.03.009 · Cited by 8 · see citing works
Personalized Transcranial Direct Current Stimulation for Behavioral and Neurophysiologic Outcomes
Bhattacharjee, S., Sivakumar, P. T., Venkatasubramanian, G., Bharath, R. D., Oishi, K., Rapp, B. C., Desmond, J. E., Chen, S. A., Sathyaprabha, T. N., Udupa, K., et al. (2025) · JAMA Network Open · doi:10.1001/jamanetworkopen.2025.26148 · Cited by 7 · see citing works
Self-citationA Literature Mini-Review of Transcranial Direct Current Stimulation in Schizophrenia
Stuchlíková, Z., & Klírová, M. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.874128 · Cited by 7 · see citing works
Stockbridge, M. D., Elm, J., Teklehaimanot, A. A., Cassarly, C. N., Spell, L. A., Fridriksson, J., & Hillis, A. E. (2023) · Neurorehabilitation and neural repair · doi:10.1177/15459683231190642 · Cited by 7 · see citing works
Personalized Dose Selection for Treatment of Patients with Neuropsychiatric Disorders Using tDCS
Bhattacharjee, S., Kashyap, R., Sreeraj, V. S., P.Sivakumar, P. S., Venkatasubramanian, G., Desmond, J. E., Chen, S. A., Sathyaprabha, T. N., & Udupa, K. (2024) · Brain Sciences · doi:10.3390/brainsci14121162 · Cited by 7 · see citing works
“Ideally, individualized montages based on head models should be used to optimize stimulation strength and location.”
Self-citationKang, D. W., Wang, S., Um, Y. H., Kim, S., Kim, T., Kim, D., Lee, C. U., & Lim, H. K. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1234086 · Cited by 7 · see citing works
“, 2020), and older females receive a higher intensity of tDCS current at the target site compared to males, which may be due to the age-dependent sex difference in tDCS current intensity resulting from cerebral atrophy (Bhattacharjee et al., 2022).”
BackgroundAzar, E. F., Shirmard, M. H., & Mirzaie, H. (2024) · Child Care Health and Development · doi:10.1111/cch.13318 · Cited by 6 · see citing works
Fathi, Y., Dissassuca, F., Ricci, G., & Liberati, G. (2025) · European Journal of Pain · doi:10.1002/ejp.70086 · Cited by 6 · see citing works
“…differences, such as skull thickness and brain morphology, along with physiological factors like hormonal fluctuations, can influence the distribution and efficacy of electrical current during stimulation (Bhattacharjee et al. 2022; Krause and Kadosh 2014; Weller et al. 2023; Zanto et al. 2021).”
Kang, D. W., Wang, S., Um, Y. H., Kim, S., Kim, T., Kim, D., Lee, C. U., & Lim, H. K. (2024) · Scientific Reports · doi:10.1038/s41598-024-67664-9 · Cited by 6 · see citing works
Kaminski, E., Maudrich, T., Bassler, P., Ordnung, M., Villringer, A., & Ragert, P. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.935781 · Cited by 6 · see citing works
“Given that there is evidence for a strong effect of sex on simulated current intensity at older ages (Bhattacharjee et al., 2022), one could speculate that tDCS application created different brain activation patterns in our male and female participants.”
BackgroundIm, C., Song, C.-B., Lee, J., Kim, D., & Seo, H. (2024) · Computer Methods and Programs in Biomedicine · doi:10.1016/j.cmpb.2024.108429 · Cited by 6 · see citing works
Gramegna, C., Franca, M., & Bolognini, N. (2025) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-025-01289-x · Cited by 5 · see citing works
“These brain differences have been shown to impact NIBS effects, including the neuromodulation of aggressive behavior (Bhattacharjee et al., 2022; Rudroff et al., 2020).”
Direct Current Stimulation Modulates Synaptic Facilitation via Distinct Presynaptic Calcium Channels
Vasu, S. O., & Kaphzan, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242316866 · Cited by 5 · see citing works
“Furthermore, previous research suggests that the current delivered to neurons during tDCS also differs by gender [65,66].”
BackgroundLi, G., McGill, M., Grant, A., Poehlmann, K., Holden, R., Brewster, S. A., & Pollick, F. E. (2025) · IEEE Transactions on Intelligent Transportation Systems · doi:10.1109/tits.2025.3578521 · Cited by 4 · see citing works
“One possible explanation for this phenomenon is that male participants may have received stronger tACS as their lower skull density could allow the electric current to penetrate more effectively compared to female participants [61].”
Xia, X., Huang, C., Chen, Z., Lei, W., & Yue, Y. (2025) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2025.104573 · Cited by 4 · see citing works
Gramegna, C., Barbieri, B., & Bolognini, N. (2025) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-025-02087-9 · Cited by 4 · see citing works
Rodgers, G., Joodaki, M., Hopf, A., Santarnecchi, E., Guzman, R. G., Müller, B., & Osmani, B. (2025) · NeuroImage · doi:10.1016/j.neuroimage.2025.121206 · Cited by 4 · see citing works
“This effect has been speculated to account for part of the variable subject response to TES noted in the literature, therefore a focus has been placed on accurate head modelling from subject MRIs and montage planning based on biophysical simulation (Menardi et al., 2022).”
InfluentialGurr, C., Splittgerber, M., Puonti, O., Siemann, J., Luckhardt, C., Pereira, H. C., Amaral, J., Crisóstomo, J., Sayal, A., Ribeiro, M., et al. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.1372-23.2024 · Cited by 4 · see citing works
Caiani, G., Chiaramello, E., Parazzini, M., Arrigoni, E., Lauro, L. R. R., Pisoni, A., & Fiocchi, S. (2025) · Bioengineering · doi:10.3390/bioengineering12060656 · Cited by 5 · see citing works
Frankel, E., Friedman, J., & Frenkel‐Toledo, S. (2025) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2025.1577899 · Cited by 3 · see citing works
Fifteen years on: a review of the Cam-CAN study of the cognitive neuroscience of ageing
Henson, R. N., & Cam‐CAN (2026) · GeroScience · doi:10.1007/s11357-026-02096-z · Cited by 4 · see citing works
Matsuura, A., Shinoda, R., Karita, T., Ishikawa, M., Yoshino, K., & Mori, F. (2023) · Neuroreport · doi:10.1097/wnr.0000000000001934 · Cited by 3 · see citing works
Evidence of physiological changes associated with single-session pre-frontal tDCS: a pilot study
Rembrandt, H. N., & Riley, E. A. (2025) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2025.1549248 · Cited by 3 · see citing works
“Patient demographics is also an area of future research, specifically age and sex, which have been shown to impact responses to tDCS in previous studies (Bhattacharjee et al., 2022; Licata et al., 2023).”
Fernandes, S. R., Callejón-Leblic, M. A., & Ferreira, H. A. (2024) · Physics in Medicine and Biology · doi:10.1088/1361-6560/ad222d · Cited by 3 · see citing works
Zhang, J., Yan, Z., Kang, A., Ouyang, J., Ma, L., Wang, X., Wu, J., Suo, D., Funahashi, S., Meng, W., et al. (2025) · Biosensors · doi:10.3390/bios15030185 · Cited by 2 · see citing works
“However, these studies did not examine variations across different age cohorts [24] or merely categorized age into basic two or three groups [26,28].”
InfluentialBetancur, D. F. A., Tarragó, M. D. G. L., França, B. R., Bueno, G. B., Gomes, J., Coelho, M. L., Venturini, C. L., Torres, I. L. D. S., Fregni, F., Bock, H., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-20769-1 · Cited by 2 · see citing works
“First , the inclusion of only female participants, intended to reduce sex-related variability in cortical excitability 52 , anatomy 53 , and descending pain modulation 54 , may limit generalizability.”
Battisti, A., Lazzaro, G., Varuzza, C., Vicari, S., & Menghini, D. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1338430 · Cited by 2 · see citing works
Franco‐Rosado, P., Callejón-Leblic, M. A., Reina‐Tosina, J., Roa, L. M., Martin‐Rodríguez, J. F., & Mir, P. (2024) · Physics in Medicine and Biology · doi:10.1088/1361-6560/ad5bb9 · Cited by 2 · see citing works
Sex differences in aging and injured brain
Williamson, J. N., & Yang, Y. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-00753 · Cited by 2 · see citing works
Multimodal response-predictor analysis for three non-invasive brain stimulation protocols
Therrien-Blanchet, J.-M., Ferland, M. C., Badri, M., Rousseau, M.-A., Merabtine, A., Boucher, E., Hofmann, L. H., Boré, A., Descoteaux, M., Lepage, J., et al. (2024) · Brain Research · doi:10.1016/j.brainres.2024.149372 · Cited by 1 · see citing works
Generalized learning induced by training and tDCS is predicted by prefrontal cortical morphology
Ehrhardt, S. E., Wards, Y., Shaw, T. B., Garner, K., Bollmann, S., Mattingley, J. B., Dux, P. E., & Filmer, H. L. (2025) · Cerebral Cortex · doi:10.1093/cercor/bhaf229 · Cited by 1 · see citing works
Fernandez, L. G., Muñoz-Gualan, P., Romero‐Ferreiro, V., Padilla, S., Moleón-Ruiz, Á., García, M. M.-B., Wynn, R., & Rodríguez–Jiménez, R. (2026) · Journal of NeuroEngineering and Rehabilitation · doi:10.1186/s12984-026-02177-2 · Cited by 1 · see citing works
Cerebellar tDCS and pain modulation: a critical integrative and systematic review
Betancur, D. F. A., Tarragó, M. D. G. L., Louzada, M. E., Peres, S. M., Torres, I. L. D. S., Fregni, F., & Caumo, W. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1681853 · Cited by 1 · see citing works
Dose standardization for transcranial electrical stimulation: an accessible approach
Toth, J., Brosnan, M. B., King, R.-J., Ivanov, B., & Arvaneh, M. (2025) · Scientific Reports · doi:10.1038/s41598-025-25649-2 · Cited by 1 · see citing works
Guo, Z., Yang, L., Li, Y., Lü, H., Qiu, R., & Zhu, X. (2026) · International Journal of Clinical and Health Psychology · doi:10.1016/j.ijchp.2026.100669 · Cited by 1 · see citing works
“…functions — for instance, impairments in cognitive flexibility have been observed primarily in males (Kalia et al., 2018; Shields et al., 2016), and (3) sex-dependent effects of tES, which may be mediated by changes in sex hormones like estrogen (Bhattacharjee et al., 2022; Lee et al., 2018).”
Soleimani, G., Wischnewski, M., Berger, T. A., Alekseichuk, I., Paulus, M. P., Lim, K. O., Ekhtiari, H., & Opitz, A. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106758 · Cited by 1 · see citing works
Kim, T., Kang, D. W., Fajardo, J. C. S., Jang, H., Um, Y. H., Kim, S., Wang, S., Kim, D., & Lim, H. K. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1356073 · Cited by 1 · see citing works
Allgemeine Wirkmechanismen der Gleichstromstimulation
Darkow, R., Sidiropoulos, K., & Kroker, C. (2025) · Springer eBooks · doi:10.1007/978-3-662-70454-7_12 · Cited by 1 · see citing works
Melahbid, S. S., Amiri, E., Tadıbı, V., & Machado, D. G. D. S. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1649732 · Cited by 1 · see citing works
Battisti, A., Lazzaro, G., Varuzza, C., Vicari, S., & Menghini, D. (2023) · medRxiv · doi:10.1101/2023.07.25.23292956
“Furthermore, it has been found that major demographic characteristics such as gender 417 (79,80) and age (81–83) could contribute to the inter-subject variability in the effects of tES.”
Fathi, Y., Dissassuca, F., Ricci, G., & Liberati, G. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.16.633370
Bhattacharjee, S., Sivakumar, P. T., Venkatasubramanian, G., Oishi, K., Tsapkini, K., Chen, S. A., Rapp, B. C., Desmond, J. E., Sathyaprabha, T. N., Udupa, K., et al. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-025-01737-3
“For safe and effective simulation, computational models have stressed the importance of adjusting the montages based on the atrophy pattern of an individual [6, 77].”
Self-citationGobbi, E., Pagnoni, I., Campana, E., Manenti, R., & Cotelli, M. (2025) · Brain Sciences · doi:10.3390/brainsci15080839
“…encompassing anatomical, hormonal, and neurophysiological factors, can significantly influence the outcomes of rTMS and tDCS, and should therefore be carefully considered when tailoring rTMS and tDCS stimulation protocols to maximise therapeutic benefits for each individual [136,138,155–161].”
Khoshchehreh, H., Tadıbı, V., Banaei, P., Jaberzadeh, S. J., Grüber, M., & Amiri, E. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.12.021
Weller, S., Derntl, B., & Plewnia, C. (2024) · Figshare · doi:10.6084/m9.figshare.26635113
Tudor, K., Labree, B., Dewey, R. S., Hoare, D. J., Kaiser, M., & Sereda, M. (2025) · Brain Sciences · doi:10.3390/brainsci16010044
“Bhattacharjee et al. [25] investigated the impact of sex differences in three age groups: young (18–40 years), middle (41–63 years), and older (64–87 years).”
Xing, S., Yuan, Y., Ren, P., Chen, Z., & Fu, Y. (2026) · Behavioural Brain Research · doi:10.1016/j.bbr.2026.116078
Çamkerten, S., Sütçübaşı, B., & Ulaşoğlu-Yıldız, Ç. (2026) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2026.113400
Acute stress alters prefrontal resting-state networks and tES restores functional connectivity
Guo, Z., Gong, Y., Qiu, R., Yang, L., Li, Y., Lü, H., & Zhu, X. (2026) · Journal of Affective Disorders · doi:10.1016/j.jad.2026.121976
Lee, C., Park, J. A., Chen, C. X., Sun, X., Kwoh, C. K., Liu, S., Miao, H., & Ahn, H. (2026) · Digital Health · doi:10.1177/20552076261456558
Sex Does Matter! The Influence of Sex on Outcomes of Transcranial Direct Current Stimulation (tDCS)
Chmiel, J., Stępień–Słodkowska, M., Kładna, A., & Niedzielska, M. (2026) · Cells · doi:10.3390/cells15161474
Ramme, A., Winter, R., Jarzebska, N., Ögel, F., Richter, M. J., Vojtěchová, I., Winter, C., Petrásek, T., Waltereit, R., & Bernhardt, N. R. (2026) · Autism Research · doi:10.1002/aur.70368
Oldrati, V., Nave, M., Boscarol, S., Ciricugno, A., Arioli, M., Cattaneo, Z., Urgesi, C., & Finisguerra, A. (2026) · Neural Plasticity · doi:10.1155/np/3295986
“Given the in fl uence of hormonal changes on synaptic plasticity [22 – 24] and possibly brain responsiveness to NIBS [21, 25, 26], we cannot exclude that variations in the menstrual cycle phase in our naturally cycling female sample may have contributed to intra-group variability or modulated the…”
Neuroanatomical predictors of frontal tDCS current distribution in cognitively healthy older adults
Busch, T. A., Stolte, S. E., Dai, Y., O’Shea, A. M., Iversen, K., Pedersen, S., Hart, G., Chen, J., Shukla, P., Albizu, A., et al. (2026) · NeuroImage · doi:10.1016/j.neuroimage.2026.122243
da Silva, E. B., de Melo, M. J. L., Mendonça, M. A., Leiros, D. D. M., Amiri, E., Faro, H., & Machado, D. G. D. S. (2026) · Neuroscience · doi:10.1016/j.neuroscience.2026.10.019
- Authors
- Bhattacharjee, S., Kashyap, R., Goodwill, A. M., O'Brien, B. A., Rapp, B., Oishi, K., Desmond, J. E., & Chen, S. H. A.
- Affiliations
- Nanyang Technological University (SG)
- National Institute of Education (SG)
- Johns Hopkins University (US)
- Corresponding author
- Kashyap, Rajan
- Goodwill, Alicia M.
- O'Brien, Beth Ann
- Rapp, Brenda
- Oishi, Kenichi
- Desmond, John E.
- Chen, S.H. Annabel
- ORCID
- Venue
- Brain Stimulation
- Publisher
- Elsevier BV
- Published
- 2022-01
- Volume
- 15
- Issue
- 1
- Pages
- 125-140
- ISSN
- 1876-4754 (ISSN-L)
- 1935-861X
- PMC
- PMC9041842
- OpenAlex
- W3217401378
- Cited by
- 80
- References
- 108
- Citations by year
- 2026: 13 · 2025: 29 · 2024: 16 · 2023: 13 · 2022: 9
- FWCI
- 3.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Brain stimulation (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DR-NTU (Nanyang Technological University) (submittedVersion, cc-by-nc-nd)
- Funders
- Department of Biotechnology, Ministry of Science and Technology, India
- Nanyang Technological University
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD103538, HD103538)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- transcranial direct current stimulation, sex differences, age differences, current density, cortical anatomy, cerebrospinal fluid volume, gray matter volume, white matter volume, inferior parietal lobule, middle frontal gyrus
- MeSH terms
- Aged, Brain, Female, Head, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Sex Characteristics, Transcranial Direct Current Stimulation
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