Category: PhD Thesis
Title of the Study: Neuroimaging correlates and Immediate effects of High-definition tDCS on persistent auditory
verbal hallucinations in schizophrenia (2016-2021).
Scientific Abstract: The thesis was a double blinded randomized, sham controlled study design designed to evaluate the efficacy of weak intensity cathodal HD-tDCS at the left temporo-parietal junction for alleviation of auditory hallucinations in patients with schizophrenia. Study comprised of a cross-sectional component where baseline structural correlates (voxel based morphometric measures and tract based morphometric measures) and functional (resting state fMRI) neural correlates of patients were compared with that of healthy controls. This study also comprised of a prospective component where changes in the clinical status as reported by the patient where corroborated with the changes in neural correlates through analysis of resting state fMRI data acquired both at baseline and post termination of the intervention.
Layman Brief: “Hearing of voices” a.k.a auditory hallucinations, are one of the most debilitating conditions that a patient suffering from schizophrenia often experiences. My study was to identify and then target a small region of the brain called the temporo-parietal junction (a small region a little above and behind the ear) with non-invasive stimulation with weak intensity direct current. This study was planned in accordance to the burgeoning evidence that this form of stimulation with a cathodal current, may lead to decrease in these symptoms. In this study, the changes in the brain activity where also looked at after the stimulation that was given over a period of 5 days, with a total of 10 sessions. This was done to understand whether the improvement or lack of improvement reported by the patient was anyway related to any specific pattern change in the brain.
Key Findings:
PhD Scholar: Dr. Rujuta Parlikar
Supervisor: Prof. Venkatasubramanian G.
Funding: ICMR-NCS fellowship, Government of India
Title of the Study: Neuroimaging correlates and Immediate effects of High-definition tDCS on persistent auditory
verbal hallucinations in schizophrenia (2016-2021).
Scientific Abstract: The thesis was a double blinded randomized, sham controlled study design designed to evaluate the efficacy of weak intensity cathodal HD-tDCS at the left temporo-parietal junction for alleviation of auditory hallucinations in patients with schizophrenia. Study comprised of a cross-sectional component where baseline structural correlates (voxel based morphometric measures and tract based morphometric measures) and functional (resting state fMRI) neural correlates of patients were compared with that of healthy controls. This study also comprised of a prospective component where changes in the clinical status as reported by the patient where corroborated with the changes in neural correlates through analysis of resting state fMRI data acquired both at baseline and post termination of the intervention.
Layman Brief: “Hearing of voices” a.k.a auditory hallucinations, are one of the most debilitating conditions that a patient suffering from schizophrenia often experiences. My study was to identify and then target a small region of the brain called the temporo-parietal junction (a small region a little above and behind the ear) with non-invasive stimulation with weak intensity direct current. This study was planned in accordance to the burgeoning evidence that this form of stimulation with a cathodal current, may lead to decrease in these symptoms. In this study, the changes in the brain activity where also looked at after the stimulation that was given over a period of 5 days, with a total of 10 sessions. This was done to understand whether the improvement or lack of improvement reported by the patient was anyway related to any specific pattern change in the brain.
Key Findings:
- The neural correlates of auditory hallucinations (evaluated through the cross-sectional component) of the study involved left temporo-parietal junction.
- There was no significant difference between the patients who received TRUE HD-tDCS versus SHAM HD-tDCS with 5 days of treatment. However, there was a significant difference in the resting state fMRI measures in the two groups suggesting a lag between stimulation based neural effects and apparent clinical changes.
- Follow up component of the study (evaluated at 3 months) showed improvement in one group over the other suggesting effects of HD-tDCS to be long term rather than immediate.
PhD Scholar: Dr. Rujuta Parlikar
Supervisor: Prof. Venkatasubramanian G.
Funding: ICMR-NCS fellowship, Government of India
Category: PhD Thesis
Title of the Study: Brain Imaging Correlates of diagnosis, persistent symptoms & Transcranial Direct Current Stimulation (tDCS) effects in Schizophrenia and Obsessive-Compulsive Disorder: A Computational Approach
Scientific Abstract: As per the report in 2017, one in seven Indians was affected by mental disorders of varying severity (197.3 million people). Despite decades of research, there are no reliable diagnostic or prognostic biomarkers for psychiatric disorders affecting the social and mental lives of many individuals. The failure to find definite predictive biomarkers is mainly due to the heterogeneity of the mental disorders and genetic, epigenetic, environmental factors, etc. Magnetic Resonance Imaging (MRI) has contributed significantly to understand the neural basis of psychiatric disorders. MRI provides detailed and high- resolution structural and functional images of the brain which is utilized to explore the disorder-specific biomarkers. One of the goals of this study was to explore the brain imaging correlates of Schizophrenia and OCD using multimodal neuroimaging and eye-tracking data. In the classification approach, we designed disorder versus disorder and disorder versus healthy controls machine learning models. For MRI data, we extracted various structural and functional features for each subject using multiple brain atlases. For eye tracking data,
we used data from three different eye tracking tasks to extract various features. Another goal of this study was to explore the brain imaging correlates of transcranial direct current stimulation effects in Schizophrenia and OCD using electric field modeling and brain entropy features from structural and functional MRI data respectively.
Layman Brief: Brain is a complex organ, controlling the behavior and function of a human being. Schizophrenia and OCD are two serious mental disorders which affect the quality of life for the patients and their relatives. It is important to investigate the predictive signatures or biomarkers in structure and function of brain regions for early diagnosis, intervention and treatment planning. The work in this study used structural and functional markers using brain MRI and eye tracking markers to create the classification models to distinguish schizophrenia and OCD from healthy subjects. Also, computer based simulation approach is implemented for understanding the electric field flow in responders and non-responders of noninvasive brain stimulation technique
Major findings and implications:
PhD Scholar: Mr. Gaurav Bhalerao
Supervisor: Prof. Venkatasubramanian G.
Funding: Candidate Supported by Department of Biotechnology (DBT), Government of India (BT/PR17316/MED/31/326/2015)
Title of the Study: Brain Imaging Correlates of diagnosis, persistent symptoms & Transcranial Direct Current Stimulation (tDCS) effects in Schizophrenia and Obsessive-Compulsive Disorder: A Computational Approach
Scientific Abstract: As per the report in 2017, one in seven Indians was affected by mental disorders of varying severity (197.3 million people). Despite decades of research, there are no reliable diagnostic or prognostic biomarkers for psychiatric disorders affecting the social and mental lives of many individuals. The failure to find definite predictive biomarkers is mainly due to the heterogeneity of the mental disorders and genetic, epigenetic, environmental factors, etc. Magnetic Resonance Imaging (MRI) has contributed significantly to understand the neural basis of psychiatric disorders. MRI provides detailed and high- resolution structural and functional images of the brain which is utilized to explore the disorder-specific biomarkers. One of the goals of this study was to explore the brain imaging correlates of Schizophrenia and OCD using multimodal neuroimaging and eye-tracking data. In the classification approach, we designed disorder versus disorder and disorder versus healthy controls machine learning models. For MRI data, we extracted various structural and functional features for each subject using multiple brain atlases. For eye tracking data,
we used data from three different eye tracking tasks to extract various features. Another goal of this study was to explore the brain imaging correlates of transcranial direct current stimulation effects in Schizophrenia and OCD using electric field modeling and brain entropy features from structural and functional MRI data respectively.
Layman Brief: Brain is a complex organ, controlling the behavior and function of a human being. Schizophrenia and OCD are two serious mental disorders which affect the quality of life for the patients and their relatives. It is important to investigate the predictive signatures or biomarkers in structure and function of brain regions for early diagnosis, intervention and treatment planning. The work in this study used structural and functional markers using brain MRI and eye tracking markers to create the classification models to distinguish schizophrenia and OCD from healthy subjects. Also, computer based simulation approach is implemented for understanding the electric field flow in responders and non-responders of noninvasive brain stimulation technique
Major findings and implications:
- The diagnosis classification models (SZ vs. HC or OCD vs. HC) of MRI data showed that the multimodal features (structural from sMRI and DTI, functional from RsfMRI) achieved the highest classification accuracies as compared to the individual modalities.
- The disorder versus disorder models (SZ vs. OCD) and related exploratory analyses showed the importance of features from diffusion imaging modalities in distinguishing the healthy subjects from the two disorders.
- The diagnosis classification models of eye-tracking data showed higher classification performance than the models of MRI data.
- The classification performances from gender-specific diagnosis classification models showed that structural features (sMRI and diffusion modality) could achieve the higher classification performances as compared to the features from RsfMRI modality.
- Our results are interesting and encouraging in a way that computational brain models and brain entropy measures can be useful for exploring the clinical outcomes of tDCS.
PhD Scholar: Mr. Gaurav Bhalerao
Supervisor: Prof. Venkatasubramanian G.
Funding: Candidate Supported by Department of Biotechnology (DBT), Government of India (BT/PR17316/MED/31/326/2015)
Category: PhD Thesis
Title of the Study: Neurobiological and Genetic Correlates of the Effect of Transcranial Direct Current Stimulation on Auditory Verbal Hallucinations in Schizophrenia (2014-2019).
Scientific Abstract: Auditory verbal hallucinations (AVH) are associated with significant distress, functional disabilities and behavioural abnormalities in schizophrenia (SCZ). Compelling functional neuroimaging evidence shows that transcranial direction current stimulation (tDCS) alters the neuroplasticity. Further, role of genetic determinants of neural plasticity has been gaining relevance for understanding the neurobiological basis of SCZ pathophysiology. In this context, PhD thesis evaluated the effect of high definition tDCS (HD-tDCS) on AVH and brain hemodynamic changes using functional near infrared spectroscopy (fNIRS). The study also evaluated the role of genetic determinants on the effect of tDCS. The study methodology included the use of high-definition tDCS (HD- tDCS), precise neuro-targeting for electrode placement, functional near infrared spectroscopy (fNIRS) and taqman 5’ nuclease assay for genotyping.
Layman Brief: Schizophrenia (SCZ) is a serious mental health condition and one of its major symptoms includes hearing of voices in the absence of any external stimuli. This state is stressful and causes impairment in daily functioning. New evidence have shown that applying small quantity of direct current to the scalp, on a targeted region can be used to help with these symptoms. It has been documented that one of the ways that stimulation with direct current works is by altering the connections inside the brain. The formation of these brain connections is guided by multiple building blocks in our DNA and any changes in these building blocks can possibly and significantly affect how much benefit the current stimulation can have. Therefore, in the PhD thesis I evaluated the effect of direct current stimulation in diminishing the voices and also the changes in connections inside the brain. Further, few relevant DNA building blocks were also evaluated to study their effect on the direct current stimulation outcome.
Major findings and implications
PhD Scholar: Dr. Harleen Chhabra
Supervisor: Prof. Venkatasubramanian G.
Funding: DBT-JRF Fellowship, Department of Biotechnology (DBT), Government of India (DBT/2015/NIMHANS/345)
Title of the Study: Neurobiological and Genetic Correlates of the Effect of Transcranial Direct Current Stimulation on Auditory Verbal Hallucinations in Schizophrenia (2014-2019).
Scientific Abstract: Auditory verbal hallucinations (AVH) are associated with significant distress, functional disabilities and behavioural abnormalities in schizophrenia (SCZ). Compelling functional neuroimaging evidence shows that transcranial direction current stimulation (tDCS) alters the neuroplasticity. Further, role of genetic determinants of neural plasticity has been gaining relevance for understanding the neurobiological basis of SCZ pathophysiology. In this context, PhD thesis evaluated the effect of high definition tDCS (HD-tDCS) on AVH and brain hemodynamic changes using functional near infrared spectroscopy (fNIRS). The study also evaluated the role of genetic determinants on the effect of tDCS. The study methodology included the use of high-definition tDCS (HD- tDCS), precise neuro-targeting for electrode placement, functional near infrared spectroscopy (fNIRS) and taqman 5’ nuclease assay for genotyping.
Layman Brief: Schizophrenia (SCZ) is a serious mental health condition and one of its major symptoms includes hearing of voices in the absence of any external stimuli. This state is stressful and causes impairment in daily functioning. New evidence have shown that applying small quantity of direct current to the scalp, on a targeted region can be used to help with these symptoms. It has been documented that one of the ways that stimulation with direct current works is by altering the connections inside the brain. The formation of these brain connections is guided by multiple building blocks in our DNA and any changes in these building blocks can possibly and significantly affect how much benefit the current stimulation can have. Therefore, in the PhD thesis I evaluated the effect of direct current stimulation in diminishing the voices and also the changes in connections inside the brain. Further, few relevant DNA building blocks were also evaluated to study their effect on the direct current stimulation outcome.
Major findings and implications
- One of the first double-blinded randomized controlled HD-tDCS trial in SCZ patients and the only study comparing the clinical benefits of HD-tDCS over conventional tDCS. However, this needs to be studied more rigorously in a cross-over design
- 5-days of twice daily, 20-minute sessions of verum HD-tDCS at left temporoparietal junction (TPJ) effectively reduced persistent auditory hallucinations in patients with SCZ even though high placebo effect was also observed.
- fNIRS is a feasible neuroimaging method to study the hemodynamic changes post HD-tDCS
- Catechol-O-methyltransferase (COMT), Brain derived neurotropic factor (BDNF) and Neuregulin1 (NRG-1) genotype had a significant effect on tDCS outcome. Therefore, alteration in genotype of neuroplasticity genes might play an important role in effective translation of tDCS induced clinical improvement and cortical modulation
PhD Scholar: Dr. Harleen Chhabra
Supervisor: Prof. Venkatasubramanian G.
Funding: DBT-JRF Fellowship, Department of Biotechnology (DBT), Government of India (DBT/2015/NIMHANS/345)
Category: PhD Thesis
Title of the Study: Cognitive, Neurophysiological & Neuroimaging Correlates Of The Effect Of Transcranial Direct Current Stimulation On Auditory Verbal Hallucinations In Schizophrenia (2013-2016)
Scientific Abstract: About 20-30% of schizophrenia patients report persistent auditory verbal hallucinations (AVH) that are refractory to antipsychotic medications. Transcranial Direct Current Stimulation (tDCS), a non-invasive and safe neuromodulatory technique, has attracted significant interest as an add-on treatment for refractory AVH in schizophrenia. Studies examining the efficacy of tDCS for refractory AVH in schizophrenia have reported inconsistent findings. In this study, using a randomized, double-blind, sham-controlled design (RCT), examined the effect of add-on tDCS [anode corresponding to left dorsolateral prefrontal cortex and cathode to left temporo-parietal junction; 2-mA, twice-daily sessions for 5-days] to treat refractory AVH in schizophrenia patients (N=25). Following this RCT phase, patients that had <30% reduction in AVH severity were offered an open-label extension (OLE) active stimulation to evaluate the effect of cross-over to verum tDCS. In the RCT phase, repeated measures ANOVA with tDCS type [verum (N=12) vs. sham (N=13)] as between subjects factor demonstrated a significant tDCS-type X time-point interaction [F=21.5, p<0.001, partial-η2=0.48] with significantly greater reduction of AVH score in verum tDCS group as compared to sham group. In the OLE phase, sham-to-verum crossed over patients (N=13) showed significantly greater reduction in AVH severity than their corresponding change during RCT phase (t=2.9; p=0.01). Together, these observations add further support to the beneficial effects of add-on tDCS to treat refractory AVH schizophrenia. These observations were corroborated by findings from neurophysiological and neuroimaging assessments.
Layman Brief: Schizophrenia is a brain disorder where a common symptom is hearing voices that others around do not hear. This symptom is called auditory verbal hallucination (AVH). In about 30% of the patients diagnosed with schizophrenia, this symptoms persists despite adequate treatment with psychiatric medication. Transcranial direct current stimulation is a safe, well-tolerated and easy to administer add-on treatment. It involves passing very low constant current (2 mA from a 9V battery) for20 minutes, twice a day for five days to brain areas responsible for the experience of AVH. At random, 12 schizophrenia patients experiencing persistent AVH received true tDCS add-on treatment and 13 schizophrenia patients experiencing persistent AVH received sham tDCS add-on treatment. None of the 13 patients receiving sham tDCS reported <30% reduction in AVH severity. Consequently, they were offered open-label true tDCS treatment for another 5 days, twice-daily session. Post open-label true tDCS treatment all the patients reported <30% reduction in AVH severity. Neuroimaging findings and changes in the brain's event-related potentials suggest that tDCS treatment causes changes in brain's circuits responsible for AVH and plasticity potential (brain's ability to change itself).
Major Findings:
PhD Scholar: Dr Anushree Bose
Supervisor: Prof. Venkatasubramanian G.
Funding: Candidate supported by Swarnajayanti-DST Fellowship awarded to the PhD Supervisor, Department of Biotechnology (DBT), Government of India (DST/SJF/LSA-02/2014-5).
Title of the Study: Cognitive, Neurophysiological & Neuroimaging Correlates Of The Effect Of Transcranial Direct Current Stimulation On Auditory Verbal Hallucinations In Schizophrenia (2013-2016)
Scientific Abstract: About 20-30% of schizophrenia patients report persistent auditory verbal hallucinations (AVH) that are refractory to antipsychotic medications. Transcranial Direct Current Stimulation (tDCS), a non-invasive and safe neuromodulatory technique, has attracted significant interest as an add-on treatment for refractory AVH in schizophrenia. Studies examining the efficacy of tDCS for refractory AVH in schizophrenia have reported inconsistent findings. In this study, using a randomized, double-blind, sham-controlled design (RCT), examined the effect of add-on tDCS [anode corresponding to left dorsolateral prefrontal cortex and cathode to left temporo-parietal junction; 2-mA, twice-daily sessions for 5-days] to treat refractory AVH in schizophrenia patients (N=25). Following this RCT phase, patients that had <30% reduction in AVH severity were offered an open-label extension (OLE) active stimulation to evaluate the effect of cross-over to verum tDCS. In the RCT phase, repeated measures ANOVA with tDCS type [verum (N=12) vs. sham (N=13)] as between subjects factor demonstrated a significant tDCS-type X time-point interaction [F=21.5, p<0.001, partial-η2=0.48] with significantly greater reduction of AVH score in verum tDCS group as compared to sham group. In the OLE phase, sham-to-verum crossed over patients (N=13) showed significantly greater reduction in AVH severity than their corresponding change during RCT phase (t=2.9; p=0.01). Together, these observations add further support to the beneficial effects of add-on tDCS to treat refractory AVH schizophrenia. These observations were corroborated by findings from neurophysiological and neuroimaging assessments.
Layman Brief: Schizophrenia is a brain disorder where a common symptom is hearing voices that others around do not hear. This symptom is called auditory verbal hallucination (AVH). In about 30% of the patients diagnosed with schizophrenia, this symptoms persists despite adequate treatment with psychiatric medication. Transcranial direct current stimulation is a safe, well-tolerated and easy to administer add-on treatment. It involves passing very low constant current (2 mA from a 9V battery) for20 minutes, twice a day for five days to brain areas responsible for the experience of AVH. At random, 12 schizophrenia patients experiencing persistent AVH received true tDCS add-on treatment and 13 schizophrenia patients experiencing persistent AVH received sham tDCS add-on treatment. None of the 13 patients receiving sham tDCS reported <30% reduction in AVH severity. Consequently, they were offered open-label true tDCS treatment for another 5 days, twice-daily session. Post open-label true tDCS treatment all the patients reported <30% reduction in AVH severity. Neuroimaging findings and changes in the brain's event-related potentials suggest that tDCS treatment causes changes in brain's circuits responsible for AVH and plasticity potential (brain's ability to change itself).
Major Findings:
- tDCS is a relatively inexpensive, safe, well-tolerated and easy to administer effective add-on treatment for persistent AVH
- Corollary discharge, that is our ability to suppress the sensory consequences of self generated actions plays a critical role in pathophysiology of AVH
- Application of fronto-temporo-parietal tDCS (20 minutes session, twice daily, 5 days) leads to the correction of deficient auditory corollary discharge in schizophrenia patients with AVH.
- Application of fronto-temporo-parietal tDCS (20 minutes session, twice daily, 5 days) leads to changes in the connectivity and plasticity of frontal and temporo-parietal regions.
PhD Scholar: Dr Anushree Bose
Supervisor: Prof. Venkatasubramanian G.
Funding: Candidate supported by Swarnajayanti-DST Fellowship awarded to the PhD Supervisor, Department of Biotechnology (DBT), Government of India (DST/SJF/LSA-02/2014-5).