WISER Neuromodulation Program

Plasticity modulation by a host of brain stimulation techniques that apply weak intensity energies (weak intensity electrical / magnetic / ultrasonic modalities) offer promise in treating psychiatric disorders through enhancement of deficient brain functions as well as amelioration of recalcitrant symptoms facilitating re-integration – these techniques are being implemented in the InSTAR clinics through a program called “Weak Intensity Stimulation for Enhancement and Re-integration” or “WISER” Neuromodulation Program.  These weak intensity brain stimulation techniques under the WISER program will include a) Electrical: Transcranial Direct Current Stimulation (tDCS), Transcranial Alternating Current Stimulation (tACS), Transcranial Pulsed Current Stimulation (tPCS),  and Transcranial Random Noise Stimulation (tRNS), Galvanic Vestibular Stimulation (GVS) and transcranial Vagal Nerve Stimulation (tVNS); b) Magnetic: Low Field Magnetic Stimulation (LFMS) and c) Ultrasonic: Transcranial Pulsed Low-intensity, Low Frequency Focused Ultrasonic Stimulation" 

Recent evidence suggests that weak intensity direct current stimulation using tDCS can lead to adaptive neuroplastic effects with potential translational implications in psychiatry.  Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity.  tDCS has adaptive neuroplastic effects and it is a safe procedure.  tDCS has been implemented in the department of psychiatry as a clinical research program since 2012.  Over the past years, more than 5000 sessions of tDCS has been completed any significant adverse effects.  

These neuromodulatory effects by this host of brain stimulation techniques that apply weak intensity stimulation through diverse modalities offer promise in treating psychiatric disorders through enhancement of deficient brain functions as well as amelioration of recalcitrant symptoms facilitating re-integration – this paradigm can be conceptualized as “Weak Intensity Stimulation for Enhancement and Re-integration” or “WISER” neuromodulation paradigm.  

Based on this WISER neuromodulation paradigm, in the year 2016 – 2017, the faculty co-ordinators of the tDCS  have expanded the range of techniques and implemented the WISER Neuromodulation Program in the department of psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru.  In addition to the clinical research services, WISER Neuromodulation program also has a strong research component to understand the neurobiological mechanisms underlying the effect of these techniques in patients as well as the neural correlates in healthy population.  

In 2016-17, newer WISER Neuromodulation techniques that are implemented include tACS, tRNS.  Also, an optimized tDCS technique – namely – High Definition tDCS [HD-tDCS] has also been initiated.  MRI-guided HD-tDCS protocol has been standardized and implementation is in process.  This MRI-guided HD-tDCS protocol will utilize precise, personalized placement of electrodes using state-of-the-art optical localization technique guided by subject-specific structural / functional MRI in combination with as computational analyses that simulate electrical activity spread in the brain to ensure “personalized, computational neuromodulation”.  

In the recent past, substantial background works on tDCS at the Department of psychiatry supported by extramural research grants have reported clinical benefits by peer-reviewed research publications. Ongoing works in the WISER Neuromodulation Program, department of psychiatry has been incorporated in International Regulatory Guidelines for tDCS.  Peer-reviewed research publications from the WISER program has reported following clinical benefits: successful implementation of tDCS for treating Schizophrenia with treatment resistant auditory hallucinations with evidence support from randomized, sham-controlled study, treatment resistant obsessive-compulsive disorder [preliminary evidence support using randomized, sham-controlled study]  improvement of insight in schizophrenia, application in a pregnant woman with schizophrenia / depression as well as booster sessions for schizophrenia and OCD.  

Clinician-Researchers from all specialty clinics in the department of psychiatry (Schizophrenia, obsessive compulsive disorder, Geriatric Psychiatry, Center for Addiction Medicine, Perinatal Psychiatry Clinic and Mood Disorders) as well as from the department of child and adolescent psychiatry have initiated clinical research studies involving WISER neuromodulation techniques with aim towards integrating this with regular clinical practice in due course.  



The following are some of the research publications from our team under the WISER Program.

WISER Program: Research Publications & Conference Presentations

  1. Venkatasubramanian G, Subramaniam A, Rakesh G, Bose A, Nawani H, Shivakumar V, Agarwal SM, Kalmady SV, Narayanaswamy JC. Neural Effects of tDCS on Auditory Verbal Hallucinations in Schizophrenia: Evaluation using high-speed eye tracking, Neurobionics 2013 Conference Proceedings Page No. 34. (Best Poster Award in NEUROBIONICS 2013, Indo-German Workshop on Neurobionics in Clinical Neurology.)
  2. Rakesh G, Shivakumar V, Subramaniam A, Nawani H, Amaresha AC, Narayanaswamy JC, Venkatasubramanian G. Monotherapy with bifocal tDCS for Schizophrenia: A Case Report. Brain Stimulation 2013 Jul;6(4):708-9.
  3. Shivakumar V, Bose A, Rakesh G, Nawani H, Subramaniam A, Agarwal SM, Kalmady SV, Narayanaswamy JC, Venkatasubramanian G. Rapid improvement of auditory verbal hallucinations in schizophrenia after add-on treatment with transcranial direct-current stimulation. J ECT. 2013 Sep;29(3):e43-4.
  4. Nawani H, Kalmady SV, Bose A, Shivakumar V, Rakesh G, Subramaniam A, Narayanaswamy JC, Venkatasubramanian G. Neural Basis of tDCS Effects on Auditory Verbal Hallucinations in Schizophrenia : A Case Report Evidence for Cortical Neuroplasticity Modulation. J ECT. 2014;30(1) e2-4.
  5. Agarwal SM, Shivakumar V, Bose A, Subramaniam A, Nawani H, Chhabra H, Kalmady SV, Narayanaswamy JC, Venkatasubramanian G. Transcranial Direct Current Stimulation in Schizophrenia – A Review. Clinical Psychopharmacology and Neuroscience 2013;11(3):118-125.
  6. Nawani H, Bose, Agarwal SM, Shivakumar V, Chhabra H, Subramaniam A, Kalmady S, Narayanaswamy JC, Venkatasubramanian G. Modulation of Corollary Discharge Dysfunction in Schizophrenia by tDCS: Preliminary Evidence. Brain Stimulation 2014;7(3):486-488.
  7. Bose A, Shivakumar V, Narayanaswamy JC, Nawani H, Subramaniam A, Agarwal SM, Chhabra H, Kalmady SV, Venkatasubramanian G. Insight facilitation with add-on tDCS in Schizophrenia. Schizophrenia Research 2014;156(1):63-65.
  8. Shivakumar V, Narayanaswamy JC, Agarwal SM, Bose A, Subramaniam A, Venkatasubramanian G. Targeted, Intermittent Booster tDCS: A Novel Add-on Application for Maintenance Treatment in a Schizophrenia Patient with Refractory Auditory Verbal Hallucinations. Asian Journal of Psychiatry 2014 Oct;11:79-80.
  9. Narayanaswamy JC, Shivakumar V, Bose A, Agarwal SM, Venkatasubramanian G, Gangadhar BN. Sustained Improvement of Negative Symptoms in Schizophrenia with Add-on tDCS: A Case Report. Clinical Schizophrenia And Related Psychoses 2014 Oct;8(3):135-6
  10. Narayanaswamy JC, Jose D, Chhabra H, Agarwal SM, Shrinivasa B, Hegde A, Bose A, Kalmady SV, Venkatasubramanian G, Reddy YCJ. Successful Application of Add-on Transcranial Direct Current Stimulation (tDCS) for Treatment of SSRI resistant OCD. Brain Stimulation 2015 May-Jun;8(3):655-7      
  11. Shivakumar V, Agarwal SM, Bose A, Kandasamy A, Rao NP, Narayanaswamy JC, Venkatasubramanian G. Safety of transcranial Direct Current Stimulation (tDCS) in Alcohol Induced Psychotic Disorder with Comorbid Psoriasis: A Case Report. Indian Journal of Psychological Medicine 2016 Jan-Feb;38(1):71-3
  12. Fregni F, Nitsche MA, Loo C, Brunoni AR, Marangolo P, Leite J, Carvalho S, Bolognini N, Caumo W, Paik NJ, Simis M, Ueda K, Hamed E, Luu P, Tucker DM, Tyler WJ, Brunelin J, Datta A, Juan CH, Venkatasubramanian G, Boggio PS, Bikson M. Regulatory considerations for the clinical and research use of transcranial direct current stimulation (tDCS): Review and recommendations from an expert panel. Clinical Research and Regulatory Affairs 2014 2015 Mar 1;32(1):22-35.
  13. Shenoy S, Bose A, Chhabra H, Dinakaran D, Agarwal SM, Shivakumar V, Narayanaswamy JC, Sivakumar PT, Venkatasubramanian G. Transcranial Direct Current Stimulation (tDCS) for Auditory Verbal Hallucinations in Schizophrenia during Pregnancy: A Case Report. Brain Stimulation 2015 Jan-Feb;8(1):163-
  14. Agarwal SM, Bose A, Shivakumar V, Narayanaswamy JC, Chhabra H, Kalmady SV, Nitsche MA, Venkatasubramanian G. Impact of antipsychotic medication on tDCS effects in schizophrenia patients. International Conference on Schizophrenia (ICONS), Chennai, 21 - 23, August, 2014. [BEST PAPER AWARD IN International Conference on Schizophrenia, Chennai, 2014]
  15. Subramaniam A, Agarwal SM, Kalmady SV, Shivakumar V, Chhabra H, Bose A, Damodharan D, Narayanaswamy JC, Hutton SB, Venkatasubramanian G. Transcranial Direct Current Stimulation (tDCS) Improves Antisaccade Task Performance in Schizophrenia. Indian Journal of Psychological Medicine 2015 Oct-Dec;37(4):419-22.
  16. Bose A, Sowmya S, Shenoy S, Agarwal SM, Chhabra H, Narayanaswamy JC, Venkatasubramanian G. Clinical Utility of Attentional Salience in Treatment of Auditory Verbal Hallucinations in Schizophrenia using Transcranial Direct Current Stimulation (tDCS). Schizophrenia Research 2015 May;164(1-3):279-80
  17. Shivakumar V, Chhabra H, Subbanna M, Agarwal SM, Bose A, Kalmady SV, Narayanaswamy JC, Debnath M, Venkatasubramanian G. Effect of tDCS on Auditory Hallucinations in Schizophrenia: Influence of Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism. Asian Journal of Psychiatry 2015 Aug;16:75-7.
  18. Chhabra H, Shivakumar V, Agarwal SM, Bose A, Venugopal D, Rajasekaran A, Subbanna M, Kalmady SV, Narayanaswamy JC, Debnath M, Venkatasubramanian G. Transcranial Direct Current Stimulation & Neuroplasticity Genes: Implications for Schizophrenia. Acta Neuropsychiatrica 2016 Feb;28(1):1-10.
  19. Agarwal SM, Bose A, Shivakumar V, Narayanaswamy JC, Chhabra H, Kalmady SV, Varambally S, Nitsche MA, Venkatasubramanian G, Gangadhar BN. Impact of antipsychotic medication on transcranial direct current stimulation (tDCS) effects in schizophrenia patients. Psychiatry Res. 2016 Jan 30;235:97-103.
  20. Sreeraj VS, Bose A, Shanbhag V, Narayanaswamy JC, Venkatasubramanian G, Benegal V. Monotherapy with tDCS for Treatment of Depressive Episode during Pregnancy: A Case Report. Brain Stimul. 2016 Mar 11. pii: S1935-861X(16)30035-3. doi: 10.1016/j.brs.2016.03.007.
  21. Hazari N, Narayanaswamy JC, Chhabra H, Bose A, Venkatasubramanian G, Janardhan Reddy YC. Response to transcranial direct current stimulation (tDCS) in a case of episodic obsessive compulsive disorder. The Journal of ECT 2016 Mar 23
  22. Agarwal SM, Rajur S, Bose A, Shenoy S, Miriyala S, Shivakumar V, Chhabra H, Narayanaswamy JC, Sivakuamar PT, Venkatasubramanian G. Use of transcranial direct current stimulation (tDCS) in a woman with behavioral variant fronto-temporal dementia. Asian Journal of Psychiatry (in press)
  23. Murugaraja Venkatachalam, Venkataram Shivakumar, Palanimuthu T Sivakumar, Preeti Sinha, Ganesan Venkatasubramanian: Transcranial Direct Current Stimulation for Mild Cognitive Impairment: A Review.
  24. Vanteemar S Sreeraj, Venkataram Shivakumar, Anushree Bose, Purohit N Abhiram, Sri Mahavir Agarwal, Harleen Chhabra, Janardhanan C Narayanaswamy, Ganesan Venkatasubramanian: A functional domain based approach in neurocognitive rehabilitation with tDCS: A case report. Clinical Psychopharmacology and Neuroscience 04/2017;
  25. V.S. Sreeraj, A. Bose, H. Chabbra, V. Shivakumar, S.M. Agarwal, C.N. Janardhanan, N.P. Rao, K. Muralidharan, S. Varambally, G. Venkatasubramanian: Effect of single-session tDCS on cognition in Schizophrenia: A randomized double-blind cross-over study. Brain Stimulation 03/2017; 10(2):429., DOI:10.1016/j.brs.2017.01.276
  26. A. Bose, H. Nawani, S.M. Agarwal, V. Shivakumar, J.C. Narayanaswamy, D. Kumar, G. Venkatasubramanian: Effect of fronto-temporal transcranial direct current stimulation on corollary discharge in schizophrenia: A randomized, double-blind, sham-controlled study. Brain Stimulation 03/2017; 10(2):411., DOI:10.1016/j.brs.2017.01.217
  27. Vanteemar S. Sreeraj, Vandita Shanbhag, Hema Nawani, Venkataram Shivakumar, Dinakaran Damodharan, Anushree Bose, Janardhanan C. Narayanaswamy, Ganesan Venkatasubramanian: Feasibility of Online Neuromodulation Using Transcranial Alternating Current Stimulation in Schizophrenia: A Case Report. Indian Journal of Psychological Medicine 03/2016; 39(1)., DOI:10.4103/0253-7176.198937
  28. Vanteemar S Sreeraj, Anushree Bose, Vandita Shanbhag, Janardhanan C. Narayanaswamy, Ganesan Venkatasubramanian, Vivek Benegal: Monotherapy with tDCS for Treatment of Depressive Episode during Pregnancy: A Case Report. Brain Stimulation 03/2016; 9(3)., DOI:10.1016/j.brs.2016.03.007
  29. Dinakaran D, Parlikar R, Sreeraj VS, Neikar A, Nagendrappa S, Shivakumar V, Venkatasubramanian G. Right-sided Transcranial Direct Current Stimulation and Attentional Salience of Auditory Hallucinations in Schizophrenia. Indian J Psychol Med. 2017 Nov-Dec;39(6):821-822.
  30. Bose A, Shivakumar V, Chhabra H, Parlikar R, Sreeraj VS, Dinakaran D, Narayanaswamy JC, Venkatasubramanian G. Feasibility and Clinical Utility of High-definition Transcranial Direct Current Stimulation in the Treatment of Persistent Hallucinations in Schizophrenia. East Asian Arch Psychiatry. 2017 Dec;27(4):162-4.
  31. Taylor ST, Chhabra H, Sreeraj VS, Shivakumar V, Kalmady SV, Venkatasubramanian G. Neural Effects of Transcranial Direct Current Stimulation in Schizophrenia: A Case Study using Functional Near-infrared Spectroscopy. Indian J Psychol Med. 2017 Sep-Oct;39(5):691-694.
  32. Murugaraja V, Shivakumar V, Sivakumar PT, Sinha P, Venkatasubramanian G. Clinical utility and tolerability of transcranial direct current stimulation in mild cognitive impairment. Asian J Psychiatr. 2017 Dec;30:135-140.
  33. Bose A, Shivakumar V, Agarwal SM, Kalmady SV, Shenoy S, Sreeraj VS, Narayanaswamy JC, Venkatasubramanian G. Efficacy of fronto-temporal transcranial direct current stimulation for refractory auditory verbal hallucinations in schizophrenia: A randomized, double-blind, sham-controlled study. Schizophr Res. 2017 Aug 30. pii: S0920-9964(17)30523-6.
  34. Chhabra, Harleen & Shivakumar, Venkataram & Subbanna, Manjula & Kalmady, Sunil & Bose, Anushree & Agarwal, S. Mahavir & Vs, Sreeraj & Damodharan, Dinakaran & C. Narayanaswamy, Janardhanan & Debnath, Monojit & Venkatasubramanian, Ganesan. (2018). Gene Polymorphisms and response to Transcranial Direct Current Stimulation for Auditory Verbal Hallucinations in Schizophrenia. Acta Neuropsychiatrica 2018 (in press)
  35. Bose A, Nawani H, Agarwal SM, Shivakumar V, Kalmady SV, Shenoy S, Sreeraj VS, Narayanaswamy JC, Kumar D, Venkatasubramanian G. Effect of fronto-temporal transcranial direct current stimulation on corollary discharge in schizophrenia: A randomized, double-blind, sham-controlled mediation analysis study. Schizophr Res. 2018 Jul 31. pii: S0920-9964(18)30486-9. doi: 10.1016/j.schres.2018.07.040
  36. Mukku SSR, Selvaraj S, Parlikar R, Damodharan D, Sivakumar PT, Nagaraj C, Mangalore S, Venkatasubramanian G, Varghese M. High-Definition Transcranial direct current stimulation (HD-tDCS) for auditory hallucinations in dementia-A case series.  Asian J Psychiatr. 2018 Oct;37:102-105.
  37. Sreeraj VS, Dinakaran D, Parlikar R, Chhabra H, Selvaraj S, Shivakumar V, Bose A, Narayanaswamy JC, Venkatasubramanian G. High-definition transcranial direct current simulation (HD-tDCS) for persistent auditory hallucinations in schizophrenia. Asian J Psychiatr. 2018 Oct;37:46-50.
  38. Gowda SM, Narayanaswamy JC, Hazari N, Bose A, Chhabra H, Balachander S, Bhaskarapillai B, Shivakumar V, Venkatasubramanian G, Reddy YCJ. Efficacy of pre-supplementary motor area transcranial direct current stimulation for treatment resistant obsessive compulsive disorder: A randomized, double blinded, sham controlled trial.  Brain Stimul. 2019 Feb 13. pii: S1935-861X(19)30058-0. doi: 10.1016/j.brs.2019.02.005.
  39. Shivakumar V, Dinakaran D, Narayanaswamy JC, Venkatasubramanian G. Noninvasive brain stimulation in obsessive-compulsive disorder. Indian J Psychiatry. 2019 Jan;61(Suppl 1):S66-S76. doi: 10.4103/psychiatry.IndianJPsychiatry_522_18.
  40. Venkatasubramanian G, Narayanaswamy JC.  Transcranial direct current stimulation in psychiatry. Lancet Psychiatry. 2019 Jan;6(1):8-9.
  41. Sreeraj VS, Bose A, Chhabra H, et al. Working memory performance with online-tDCS in schizophrenia: A randomized, double-blinded, sham-controlled, partial cross-over proof-of-concept study. Asian journal of psychiatry 2020;50:101946.
  42. Thimmashetty VH, Parlikar R, Selvaraj S, et al. Target specific effects of direct current stimulation in schizo-obsessive disorder: A case report. Brain stimulation 2020;13(3):858-860.
  43. Chhabra H, Bose A, Shivakumar V, et al. Tolerance of transcranial direct current stimulation in psychiatric disorders: An analysis of 2000+ sessions. Psychiatry research 2020;284:112744.
  44. Holla B, Biswal J, Ramesh V, et al. Effect of prefrontal tDCS on resting brain fMRI graph measures in Alcohol Use Disorders: A randomized, double-blind, sham-controlled study. Progress in neuro-psychopharmacology & biological psychiatry 2020;102:109950.
  45. Sarma Sreepada SS, Baliga SP, Naik SS, et al. Dual stimulation with tDCS-iTBS as add-on treatment in recurrent depressive disorder-a case report. Brain stimulation 2020;13(3):625-626.
  46. Bhalerao GV, Sreeraj VS, Bose A, Narayanaswamy JC, Venkatasubramanian G. Comparison of electric field modeling pipelines for transcranial direct current stimulation. Neurophysiologie clinique = Clinical neurophysiology 2021;51(4):303-318.
  47. Chhabra H, Thimmashetty VH, Shivakumar V, Venkatasubramanian G, Narayanswamy JC. Effect of transcranial direct current stimulation on in-vivo assessed neuro-metabolites through magnetic resonance spectroscopy: a systematic review. Acta neuropsychiatrica 2021:1-12.
  48. Fregni F, El-Hagrassy MM, Pacheco-Barrios K, … Venkatasubramanian G, …et al. Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders. The international journal of neuropsychopharmacology 2021;24(4):256-313.
  49. Rangarajan SK, Suhas S, Reddy MSS, Sreeraj VS, Sivakumar PT, Venkatasubramanian G. Domiciliary tDCS in Geriatric Psychiatric Disorders: Opportunities and Challenges. Indian journal of psychological medicine 2021;43(4):351-356.
  50. Selvaraj S, Chhabra H, Dinakaran D, Sreeraj VS, Venkataram S, Narayanaswamy JC, Kesavan M, Varambally S, Venkatasubramanian G. Auditory signal detection in schizophrenia: Correlates with auditory verbal hallucinations & effect of single session transcranial direct current stimulation (tDCS). Psychiatry Res. 2021;297:113704. doi: 10.1016/j.psychres.2021.113704.
  51. Thamby A, Seshachala K, Sharma L, Thimmashetty VH, Balachander S, Shivakumar V, Hazari N, Chhabra H, Arumugham SS, Ts J, K M, Venkatasubramanian G, Reddy YCJ, Narayanaswamy JC. Transcranial direct current stimulation for treatment-resistant obsessive-compulsive disorder-A large case series. Asian J Psychiatr. 2021 Jun;60:102625. doi: 10.1016/j.ajp.2021.102625. Epub 2021 Apr 5. PMID: 33930710.