Browsing by Author "Rajan, R"

Now showing 1 - 5 of 5
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    Changing Patterns of Stroke Awareness among Primary Care Physicians: Results of an Ongoing Study from Kerala, India
    (CEREBROVASCULAR DISEASES, 2016) Sukumaran, S; Maniangat, S; Khan, F; Vt, J; Rajan, R
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    Cortical plasticity and levodopa-induced dyskinesias in Parkinson's disease: Connecting the dots in a multicomponent network
    (Clin Neurophysiol., 2017-06) Rajan, R; Popa, T; Quartarone, A; Ghilardi, MF; Kishore, A
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    Dopamine D3 receptor Ser9Gly variant is associated with impulse control disorders in Parkinson's disease patients
    (Parkinsonism Relat Disord., 2016-12) Krishnamoorthy, S; Rajan, R; Banerjee, M; Kumar, H; Sarma, G; Krishnan, S; Sarma, S; Kishore, A
    Introduction: Impulse control disorders (ICD) are reported to occur at variable frequencies in different ethnic groups. Genetic vulnerability is suspected to underlie the individual risk for ICD. We investigated whether the allelic variants of dopamine (DRD3), glutamate (GRIN2B) and serotonin (HTR2A) receptors are linked to ICD in Indian Parkinson’s disease (PD) patients. Methods: We conducted a prospective, case-control study which included PD patients (70 with ICD, 100 without ICD categorized after direct psychiatric interview of patient and caregiver) and 285 healthy controls. Single nucleotide polymorphism (SNP) variants of DRD3 p.S9G (rs6280), GRIN2B c.2664C>T (rs1806201) and HTR2A c.102T>C (rs6313) were genotyped. Results: Multivariate regression analysis revealed that DRD3 p.Ser9Gly (rs6280) heterozygous variant CT (OR ¼ 2.22, 95% CI: 1.03e4.86, p ¼ 0.041), higher daily Levodopa equivalent doses (LED) of drugs (for 100 mg LED, OR ¼ 1.14, 95% CI: 1.01e1.29, p ¼ 0.041), current dopamine agonist but not Levodopa use (OR ¼ 2.16, 95% CI: 1.03e4.55, p ¼ 0.042) and age of onset of motor symptoms under 50 years (OR 2.09, 95% CI: 1.05e4.18, p ¼ 0.035) were independently associated with ICD. Conclusion: DRD3 p.Ser9Gly (rs6280) CT genotype is associated with ICD in Indian PD patients and this association is novel. Enhanced D3 receptor affinity due to gain-of-function conferred by the glycine residues could impair reward-risk assessment in the mesolimbic system and contribute to development of impulsive behaviour, in carriers of this genotype.
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    Electrode Position and Current Amplitude Modulate Impulsivity after Subthalamic Stimulation in Parkinsons Disease-A Computational Study
    (FRONTIERS IN PHYSIOLOGY, 2016) Mandali, A; Chakravarthy, VS; Rajan, R; Sarma, S; Kishore, A
    Background: Subthalamic Nucleus Deep Brain Stimulation (SIN-DES) is highly effective in alleviating motor symptoms of Parkinson's disease (PD) which are not optimally controlled by dopamine replacement therapy. Clinical studies and reports suggest that STN-DBS may result in increased impulsivity and de novo impulse control disorders (ICD). Objective/Hypothesis: We aimed to compare performance on a decision making task, the Iowa Gambling Task (IGT), in healthy conditions (HC), untreated and medically-treated PD conditions with and without STN stimulation. We hypothesized that the position of electrode and stimulation current modulate impulsivity after STN-DBS. Methods: We built a computational spiking network model of basal ganglia (BG) and compared the model's STN output with STN activity in PD. Reinforcement learning methodology was applied to simulate IGT performance under various conditions of dopaminergic and STN stimulation where IGT total and bin scores were compared among various conditions. Results: The computational model reproduced neural activity observed in normal and PD conditions. Untreated and medically-treated PD conditions had lower total IGT scores (higher impulsivity) compared to HC (P < 0.0001). The electrode position that happens to selectively stimulate the part of the STN corresponding to an advantageous panel on IGT resulted in de-selection of that panel and worsening of performance (P < 0.0001). Supratherapeutic stimulation amplitudes also worsened IGT performance (P < 0.001). Conclusion(s): In our computational model, STN stimulation led to impulsive decision making in IGT in PD condition. Electrode position and stimulation current influenced impulsivity which may explain the variable effects of STN-DBS reported in patients.
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    Malignant Subthalamic Nucleus-Deep Brain Stimulation Withdrawal Syndrome in Parkinson's Disease
    (Mov Disord Clin Pract, 2016-03) Rajan, R; Krishnan, S; Kesavapisharady, KK; Kishore, A