Guide: Dr. Bindu M Kutty
Co-guide: Dr. John P John (Addl. Prof., Dept. of Psychiatry)
Neurophysiology @ NIMHANS |
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Arun Sasidharan (5th yr PhD Scholar) presented his PhD work titled "Aberrant neural synchrony in Schizophrenia: a multi-modal EEG, fMRI and Polysomnography study"
Guide: Dr. Bindu M Kutty Co-guide: Dr. John P John (Addl. Prof., Dept. of Psychiatry) Arun Sasidharan (PhD Scholar) presented the paper by Ford etal from the journal Schizophrenia Bulletin 2013 entitled "Did I Do That? Abnormal Predictive Processes in Schizophrenia When Button Pressing to Deliver a Tone "
ABSTRACT Motor actions are preceded by an efference copy of the motor command, resulting in a corollary discharge of the expected sensation in sensory cortex. These mechanisms allow animals to predict sensations, suppress responses to self-generated sensations, and thereby process sensations efficiently and economically. During talking, patients with schizophrenia show less evidence of pretalking activity and less suppression of the speech sound, consistent with dysfunction of efference copy and corollary discharge, respectively. We asked if patterns seen in talking would generalize to pressing a button to hear a tone, a paradigm translatable to less vocal animals. In 26 patients [23 schizophrenia, 3 schizoaffective (SZ)] and 22 healthy controls (HC), suppression of the N1 component of the auditory event–related potential was estimated by comparing N1 to tones delivered by button presses and N1 to those tones played back. The lateralized readiness potential (LRP) associated with the motor plan preceding presses to deliver tones was estimated by comparing right and left hemispheres’ neural activity. The relationship between N1 suppression and LRP amplitude was assessed. LRP preceding button presses to deliver tones was larger in HC than SZ, as was N1 suppression. LRP amplitude and N1 suppression were correlated in both groups, suggesting stronger efference copies are associated with stronger corollary discharges. SZ have reduced N1 suppression, reflecting corollary discharge action, and smaller LRPs preceding button presses to deliver tones, reflecting the efference copy of the motor plan. Effects seen during vocalization largely extend to other motor acts more translatable to lab animals. Dr Harsha HN successfully defended his PhD work entitled "Neurobiology of Auditory Verbal Hallucinations in Schizophrenia - An integrated fMRI, EEG and Genomics based approach".
Guide: Dr Bindu M Kutty (Prof, Neurophysiology) Co-Guides: Dr Sanjeev Jain (Prof, Psychiatry) and Dr John P John (Additional Prof, Psychiatry) Examiner: Dr K Srinivasan (Dean, St John's Research Institute and Professor of Psychiatry) Kumari Anshu Jha (2nd year PhD scholar) presented her seminar on "Interneuron dysfunction in neuropsychiatric disorders". She focused on GABAergic dysfunction in Schizophrenia and Autism.
Anshu gave an overview of Interneuron functions (feedback & feedforward inhibition, network oscillations and synchrony, modulation of excitability, integration and cortical development and plasticity) and then highlighted the complexity of internuron types (classified based on morphological, molecular, electrophysiological properties - eg Markram 2004). She then discussed the role of GABAergic neurons in the pathophysiology of Schizophrenia and then Autism from post-mortem studies and animal models (gene knockouts) while showing that GABA impairment seems to be present in a wide variety of neuropsychiatric disorders. She then went through the mechanisms through which these interneurons modulate network oscillations via electrical gap junctions and neurochemical modulations amongst the interneurons (for example Parvalbumin expressing basket cells impact gamma oscillations while somatostatin expressing interneurons impact beta oscillations). Considering that the type of impairment is similar for schizophrenia and autism, the timing of the impairment seems to be a differentiator between these two disorders. Autism is seen in early childhood (diagnosed around 3 years of age when neuronal pruning is still ongoing) and the first onset of Schizophrenia happens in adolescence (when the neurons are fully formed but the myelination is still an ongoing process). Neethi Prem (2nd year PhD scholar) presented the progress on animal models of Schizophrenia
Dr Arun Sasidharan (3rd Year PhD Scholar) presented his seminar on Schizophrenia - what EEG and fMRI can tell us?
In this detailed and well spelt-out seminar, Arun started off with reviewing current research on Schizophrenia and the findings from EEG and fMRI studies in the field. He then described the classical view of Schizophrenia and then went for a deep dive into understanding how EEG, ERP, source localization and fMRI approaches work, the potential pitfalls to watchout for and the benefits of each approach in order to be able to interpret the results better. Neethi Prem (2nd year PhD Scholar) presented her seminar on "Implication of GABAergic Interneuron dysfunction in Psychiatric Disorders".
Neethi's focus was on Schizophrenia and in particular on the Parvalbumin expressing Basket (axo-somatic) and Chandelier (axo-axonal) interneurons that are fast spiking and impact Gamma synchrony. Both the number of GABAergic interneurons and the expression of GABA decreases with Schizophrenia. There is reduced spine density as well as reduction in the dendritic arborization. In Basket cells, there is reduced expression of Parvalbumin, GAD67 (an isoform of the enzyme that synthesizes GABA) and GAT (the transporter). She explored the neurodevelopmental hypothesis and genetic predisposition to Schizophrenia via Receptor-Tyrosine protein kinase ERBB4 (expressed embryonically and postnatally), Neuregulin1 (NRG1, a chemoattractant) and DISC1 (a scaffolding protein). Since the GABAergic interneurons sculpt the firing pattern of the pyramidal neurons, dysfunction of these interneurons disrupts the excitatory-inhibitory balance. Gamma synchrony is said to be important in working memory and executive functions and irregularities here probably lead to corresponding cognitive deficits that are the distinctive feature of Schizophrenia. Dr. Arun Sasi (2nd year PhD scholar) presented the first seminar of this academic year. He spoke on the topic "Neurobiology of Schizophrenia". He presented a broad introduction to the range of symptoms, classification, diagnostic criteria and current hypotheses ranging from behavioural to pathophysiology, neuropharmacology, neurochemistry and genetics. The key focus was on the developmental aspects.
We had a good round of questions and robust discussions and series of follow up discussions. A great start to the seminar series and journal clubs that Dr. Shankarnarayana Rao has lined up for the year. |
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August 2019
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