{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:48:39Z","timestamp":1787863719169,"version":"build-2784847793"},"reference-count":46,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi250738-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Transcranial direct current stimulation (tDCS) is emerging as a home-based intervention for neuropsychiatric conditions and cognitive enhancement. However, its effectiveness is limited by interindividual variability, as fixed-dose protocols have failed to account for anatomic differences influencing current delivery to targeted regions and treatment outcome. While computational modeling supports individualized dosing to improve consistency, experimental validation remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi250738-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To compare the behavioral and neurophysiologic outcomes of fixed-dose vs individualized-dose tDCS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi250738-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This comparative effectiveness study using a within-participant, double-masked, crossover design was conducted from January 1, to March 31, 2024, at the National Institute of Mental Health and Neurosciences in India. Adult participants (aged 21-35 years) received 3 sessions of tDCS (fixed-dose, individualized-dose, and sham stimulation) in counterbalanced order. Individualized doses were calculated using a custom-built simulation toolbox.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi250738-7\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Behavioral performance was measured using reaction time during a rapid naming task. Neurophysiologic effects were assessed using motor-evoked potentials (MEPs) recorded before and after stimulation. Linear mixed-effects models were used for the statistical analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi250738-8\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sixteen right-hand-dominant, bilingual English-Dravidian speakers (mean [SD] age, 23.1 [3.9] years; 8 female [50%]) were included. Individualized-dose tDCS associated with significantly greater reaction time improvement over sham (estimated marginal mean [SD]: before, 753.0 [41.1] ms; after, 619.0 [41.1] ms; change [\u0394]\u2009=\u2009133.6 ms; SE,\u200910.2 ms;\n                      <jats:italic>z<\/jats:italic>\n                      \u2009score ratio, 13.09) compared with fixed-dose tDCS (before, 694.0 [41.1] ms; after, 680.0 [41.1] ms; \u0394\u2009=\u200914.6 ms; SE,\u200910.1 ms;\n                      <jats:italic>z<\/jats:italic>\n                      score ratio, 1.45). Variability was lower with individualized-dose stimulation (coefficient of variation, \u22121.14 vs 0.39 fixed vs individualized dose, respectively). Sex-stratified analyses showed that women had improvements with both fixed (\u0394\u2009=\u200958.0 ms;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.003) and individualized (\u0394\u2009=\u2009113.8 ms;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001) stimulation, while men had improvement only with individualized tDCS (\u0394\u2009=\u2009153.4 ms;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001). Seven participants (5 men and 2 women) converted from nonresponders to responders with individualized dosing. For MEPs, individualized-dose tDCS showed greater poststimulation amplitude increases over sham (\u03b2\u2009[SE], 0.91 [0.23]), although fixed-dose tDCS poststimulation amplitude was smaller, but significant (\u03b2 [SE],\u20090.56\u2009[0.23];\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.02) and showed a higher percentage change (\u03b2\u2009[SE], 144.26%\u2009[55.74%];\n                      <jats:italic>P<\/jats:italic>\n                      = .01) and reduced variability (coefficient of variation,\u2009\u22120.79 vs 1.12 [fixed]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi250738-9\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>In this comparative effectiveness study, dose-controlled tDCS was associated with consistent behavioral and neurophysiologic improvement, highlighting its translational importance in the treatment of neuropsychiatric disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.26148","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T15:31:05Z","timestamp":1756135865000},"page":"e2526148","source":"Crossref","is-referenced-by-count":8,"title":["Personalized Transcranial Direct Current Stimulation for Behavioral and Neurophysiologic Outcomes"],"prefix":"10.1001","volume":"8","author":[{"given":"Sagarika","family":"Bhattacharjee","sequence":"first","affiliation":[{"name":"Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bengaluru, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palanimuthu T.","family":"Sivakumar","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesan","family":"Venkatasubramanian","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose Dawn","family":"Bharath","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Oishi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Rapp","sequence":"additional","affiliation":[{"name":"Department of Cognitive Science, Johns Hopkins University, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Desmond","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. H. Annabel","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Psychology, School of Social Sciences, Nanyang Technological University, Singapore"},{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore"},{"name":"Centre for Research and Development in Learning, Nanyang Technological University, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. N.","family":"Sathyaprabha","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bengaluru, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaviraja","family":"Udupa","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bengaluru, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajan","family":"Kashyap","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"issue":"3","key":"zoi250738r1","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1176\/appi.ajp.20240083","article-title":"Spaced transcranial direct current stimulation for major depression.","volume":"182","author":"Couture","year":"2025","journal-title":"Am J Psychiatry"},{"issue":"1","key":"zoi250738r2","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/s41591-024-03305-y","article-title":"Home-based transcranial direct current stimulation treatment for major depressive disorder: a fully remote phase 2 randomized sham-controlled trial.","volume":"31","author":"Woodham","year":"2025","journal-title":"Nat Med"},{"issue":"5","key":"zoi250738r3","doi-asserted-by":"publisher","first-page":"522","DOI":"10.3390\/brainsci12050522","article-title":"Inter-individual variability in tDCS effects: a narrative review on the contribution of stable, variable, and contextual factors.","volume":"12","author":"Vergallito","year":"2022","journal-title":"Brain Sci"},{"issue":"5","key":"zoi250738r4","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1016\/j.brs.2015.05.002","article-title":"Inter-subject variability in electric fields of motor cortical tDCS.","volume":"8","author":"Laakso","year":"2015","journal-title":"Brain Stimul"},{"key":"zoi250738r5","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.neuroimage.2015.01.033","article-title":"Determinants of the electric field during transcranial direct current stimulation.","volume":"109","author":"Opitz","year":"2015","journal-title":"Neuroimage"},{"issue":"1","key":"zoi250738r6","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.brs.2019.10.004","article-title":"Dose-controlled tDCS reduces electric field intensity variability at a cortical target site.","volume":"13","author":"Evans","year":"2020","journal-title":"Brain Stimul"},{"issue":"12","key":"zoi250738r7","doi-asserted-by":"publisher","first-page":"2767","DOI":"10.1093\/cercor\/bhp055","article-title":"Where is the semantic system? a critical review and meta-analysis of 120 functional neuroimaging studies.","volume":"19","author":"Binder","year":"2009","journal-title":"Cereb Cortex"},{"issue":"2","key":"zoi250738r8","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1016\/j.neuroimage.2012.04.062","article-title":"A review and synthesis of the first 20 years of PET and fMRI studies of heard speech, spoken language and reading.","volume":"62","author":"Price","year":"2012","journal-title":"Neuroimage"},{"issue":"6","key":"zoi250738r9","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1016\/j.brs.2015.07.031","article-title":"Inter- and intra-individual variability in response to transcranial direct current stimulation (tDCS) at varying current intensities.","volume":"8","author":"Chew","year":"2015","journal-title":"Brain Stimul"},{"key":"zoi250738r10","doi-asserted-by":"publisher","first-page":"181","DOI":"10.3389\/fncel.2015.00181","article-title":"The contribution of interindividual factors to variability of response in transcranial direct current stimulation studies.","volume":"9","author":"Li","year":"2015","journal-title":"Front Cell Neurosci"},{"key":"zoi250738r11","doi-asserted-by":"publisher","DOI":"10.1016\/j.bandl.2020.104850","article-title":"Reading proficiency influences the effects of transcranial direct current stimulation: evidence from selective modulation of dorsal and ventral pathways of reading in bilinguals.","volume":"210","author":"Bhattacharjee","year":"2020","journal-title":"Brain Lang"},{"issue":"5","key":"zoi250738r12","doi-asserted-by":"publisher","DOI":"10.1088\/1741-2552\/aba6dc","article-title":"i-SATA: a MATLAB based toolbox to estimate current density generated by transcranial direct current stimulation in an individual brain.","volume":"17","author":"Kashyap","year":"2020","journal-title":"J Neural Eng"},{"issue":"9","key":"zoi250738r13","doi-asserted-by":"publisher","first-page":"940","DOI":"10.3390\/jpm11090940","article-title":"Focality-oriented selection of current dose for transcranial direct current stimulation.","volume":"11","author":"Kashyap","year":"2021","journal-title":"J Pers Med"},{"key":"zoi250738r14","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2022.952602","article-title":"Variation of cerebrospinal fluid in specific regions regulates focality in transcranial direct current stimulation.","volume":"16","author":"Kashyap","year":"2022","journal-title":"Front Hum Neurosci"},{"issue":"1","key":"zoi250738r15","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.brs.2021.11.018","article-title":"Sex difference in tDCS current mediated by changes in cortical anatomy: a study across young, middle and older adults.","volume":"15","author":"Bhattacharjee","year":"2022","journal-title":"Brain Stimul"},{"issue":"2","key":"zoi250738r16","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.brs.2018.12.885","article-title":"Could tDCS modulate bilingual reading?","volume":"12","author":"Bhattacharjee","year":"2019","journal-title":"Brain Stimul"},{"issue":"1","key":"zoi250738r17","doi-asserted-by":"publisher","first-page":"19715","DOI":"10.1038\/s41598-024-68691-2","article-title":"Alignment of behaviour and tDCS stimulation site induces maximum response: evidence from online tDCS and ERP.","volume":"14","author":"Bhattacharjee","year":"2024","journal-title":"Sci Rep"},{"issue":"10","key":"zoi250738r18","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1212\/WNL.57.10.1899","article-title":"Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans.","volume":"57","author":"Nitsche","year":"2001","journal-title":"Neurology"},{"issue":"19","key":"zoi250738r19","doi-asserted-by":"publisher","first-page":"6124","DOI":"10.1523\/JNEUROSCI.0728-09.2009","article-title":"Dose-dependent inverted U-shaped effect of dopamine (D2-like) receptor activation on focal and nonfocal plasticity in humans.","volume":"29","author":"Monte-Silva","year":"2009","journal-title":"J Neurosci"},{"issue":"1","key":"zoi250738r20","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.brs.2023.01.266","article-title":"The role of circadian preferred time of day and sleep pressure in tDCS-induced neuroplasticity and associated cognition.","volume":"16","author":"Salehinejad","year":"2023","journal-title":"Brain Stimul"},{"issue":"1","key":"zoi250738r21","doi-asserted-by":"publisher","first-page":"12178","DOI":"10.1038\/s41598-019-47654-y","article-title":"Simulation analyses of tDCS montages for the investigation of dorsal and ventral pathways.","volume":"9","author":"Bhattacharjee","year":"2019","journal-title":"Sci Rep"},{"issue":"12","key":"zoi250738r22","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.3390\/brainsci14121162","article-title":"Personalized dose selection for treatment of patients with neuropsychiatric disorders using tDCS.","volume":"14","author":"Bhattacharjee","year":"2024","journal-title":"Brain Sci"},{"issue":"5","key":"zoi250738r23","doi-asserted-by":"publisher","DOI":"10.1088\/1741-2552\/ab208d","article-title":"Realistic volumetric-approach to simulate transcranial electric stimulation-ROAST-a fully automated open-source pipeline.","volume":"16","author":"Huang","year":"2019","journal-title":"J Neural Eng"},{"issue":"6","key":"zoi250738r24","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1111\/j.0954-6820.1943.tb11253.x","article-title":"Measurements of the specific resistance of the human body to direct current.","volume":"114","author":"Burger","year":"1943","journal-title":"Acta Med Scand"},{"issue":"3","key":"zoi250738r25","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/BF02474537","article-title":"The specific resistance of biological material\u2013a compendium of data for the biomedical engineer and physiologist.","volume":"5","author":"Geddes","year":"1967","journal-title":"Med Biol Eng"},{"issue":"7","key":"zoi250738r26","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1109\/TBME.2003.813548","article-title":"Computation of electric and magnetic stimulation in human head using the 3-D impedance method.","volume":"50","author":"Nadeem","year":"2003","journal-title":"IEEE Trans Biomed Eng"},{"issue":"11","key":"zoi250738r27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0141417","article-title":"Language and memory improvements following tDCS of left lateral prefrontal cortex.","volume":"10","author":"Hussey","year":"2015","journal-title":"PLoS One"},{"issue":"8","key":"zoi250738r28","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1136\/jnnp-2012-302825","article-title":"Transcranial direct current stimulation (tDCS) and language.","volume":"84","author":"Monti","year":"2013","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"3","key":"zoi250738r29","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1097\/YCT.0000000000000539","article-title":"Transcranial direct current stimulation in neurodegenerative disorders.","volume":"34","author":"Pellicciari","year":"2018","journal-title":"J ECT"},{"key":"zoi250738r30","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.cortex.2016.10.016","article-title":"Limits to tDCS effects in language: failures to modulate word production in healthy participants with frontal or temporal tDCS.","volume":"86","author":"Westwood","year":"2017","journal-title":"Cortex"},{"issue":"2","key":"zoi250738r31","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1016\/j.neuroimage.2012.01.024","article-title":"Brain templates and atlases.","volume":"62","author":"Evans","year":"2012","journal-title":"Neuroimage"},{"issue":"9","key":"zoi250738r32","doi-asserted-by":"publisher","first-page":"940","DOI":"10.3390\/jpm11090940","article-title":"Focality-oriented selection of current dose for transcranial direct current stimulation.","volume":"11","author":"Kashyap","year":"2021","journal-title":"J Pers Med"},{"issue":"5","key":"zoi250738r33","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1016\/j.clinph.2012.01.010","article-title":"A practical guide to diagnostic transcranial magnetic stimulation: report of an IFCN committee.","volume":"123","author":"Groppa","year":"2012","journal-title":"Clin Neurophysiol"},{"issue":"6","key":"zoi250738r34","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/0168-5597(93)90115-6","article-title":"Variability of motor potentials evoked by transcranial magnetic stimulation.","volume":"89","author":"Kiers","year":"1993","journal-title":"Electroencephalogr Clin Neurophysiol"},{"key":"zoi250738r35","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.neuroscience.2016.02.012","article-title":"Minimum number of trials required for within- and between-session reliability of TMS measures of corticospinal excitability.","volume":"320","author":"Goldsworthy","year":"2016","journal-title":"Neuroscience"},{"key":"zoi250738r36","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.clinph.2024.12.009","article-title":"Accurate determination of motor evoked potential amplitude in TMS: the impact of personal and experimental factors.","volume":"170","author":"Nuyts","year":"2025","journal-title":"Clin Neurophysiol"},{"issue":"2","key":"zoi250738r38","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.jcm.2016.02.012","article-title":"A guideline of selecting and reporting intraclass correlation coefficients for reliability research.","volume":"15","author":"Koo","year":"2016","journal-title":"J Chiropr Med"},{"key":"zoi250738r39","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.neuropsychologia.2015.01.033","article-title":"Variability of behavioural responses to transcranial magnetic stimulation: origins and predictors.","volume":"74","author":"Nicolo","year":"2015","journal-title":"Neuropsychologia"},{"issue":"2","key":"zoi250738r40","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1097\/00004691-199603000-00007","article-title":"Cortical excitability and response variability of transcranial magnetic stimulation.","volume":"13","author":"van der Kamp","year":"1996","journal-title":"J Clin Neurophysiol"},{"key":"zoi250738r41","doi-asserted-by":"publisher","DOI":"10.1016\/j.cobeha.2024.101360","article-title":"Recent advancements in optimising transcranial electrical stimulation: reducing response variability through individualised stimulation.","volume":"56","author":"Wansbrough","year":"2024","journal-title":"Curr Opin Behav Sci"},{"issue":"1","key":"zoi250738r42","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.brs.2019.08.014","article-title":"Feasibility of home-based, self-applied transcranial direct current stimulation to enhance motor learning in middle-aged and older adults.","volume":"13","author":"Maceira-Elvira","year":"2020","journal-title":"Brain Stimul"},{"issue":"5","key":"zoi250738r43","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.brs.2016.06.004","article-title":"Safety of transcranial direct current stimulation: evidence based update 2016.","volume":"9","author":"Bikson","year":"2016","journal-title":"Brain Stimul"},{"key":"zoi250738r44","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3389\/fnsys.2014.00025","article-title":"Not all brains are created equal: the relevance of individual differences in responsiveness to transcranial electrical stimulation.","volume":"8","author":"Krause","year":"2014","journal-title":"Front Syst Neurosci"},{"issue":"3","key":"zoi250738r45","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.brs.2014.02.004","article-title":"Inter-individual variability in response to non-invasive brain stimulation paradigms.","volume":"7","author":"L\u00f3pez-Alonso","year":"2014","journal-title":"Brain Stimul"},{"key":"zoi250738r46","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.neuroimage.2013.02.049","article-title":"Targeted transcranial direct current stimulation for rehabilitation after stroke.","volume":"75","author":"Dmochowski","year":"2013","journal-title":"Neuroimage"},{"key":"zoi250738r37","unstructured":"Strategic initiatives. ISPOR. Accessed May 23, 2025. https:\/\/www.ispor.org\/strategic-initiatives"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2837962\/bhattacharjee_2025_oi_250738_1755278691.26792.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T15:31:06Z","timestamp":1756135866000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2837962"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,25]]},"references-count":46,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2025.26148","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,25]]}}}