Centre for Neuroscience Studies Graduate Theses

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    Pre-Stroke Frailty Measured by The Clinical Frailty Scale Can Predict Post-Stroke Disability
    Reehal, Kiran K.; Neuroscience Studies; Appireddy, Ramana; Walia, Jagdeep
    Background and Aims: The aim of this study was to determine the association of pre-stroke frailty, measured using the Clinical Frailty Scale (CFS) with post-stroke disability, measured using the modified Rankin Scale (mRS) at 3 months. Methods: This single centre prospective cohort study included imaging confirmed ischemic stroke patients admitted to Kingston Health Sciences Centre between January 2022 and February 2023. Frailty was categorized as non-frail (CFS: 0-4) or frail (CFS: 5-9), and post-stroke disability was a mRS score of 3-6. The statistical analysis was done using SPSS. Descriptive statistics followed by binary logistic regression were performed to assess the association between pre-stroke frailty and post-stroke disability. The covariates for testing this association were selected based on a priori knowledge and the literature. Results: 459 stroke patients were included in the study with a median (IQR) age of 76 (65-84) years and 230 (50.1%) patients were male. The prevalence of pre-stroke frailty (based on the CFS) and post-stroke disability (based on mRS) was 199 (43.4%) and 245 (53.4%), respectively. Pre-stroke frailty was strongly associated with post-stroke disability with a crude odds ratio (OR) of 10.35 (95% CI:6.61-16.23) and OR adjusted for age, sex, COPD, dementia, heart disease, stroke, and cancer was 6.52 (95% CI:3.98-10.69). Conclusions: Pre-stroke frailty measured using the CFS is an important predictor of stroke disability at 3 months and should be incorporated in the clinical decision-making pathway. Further exploration of pre-stroke frailty and its interaction with various hyperacute stroke treatments is warranted.
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    Brain-Derived Neurotrophic Factor, Stress and Inflammation Changes Associated with Therapeutic Improvement in Individuals with Schizophrenia Undergoing CBT for Psychosis
    Farcas, Adriana M.; Neuroscience Studies; Iftene, Felicia
    Background: Schizophrenia is a severe psychiatric disorder caused by the interaction of genetic and environmental factors, its pathogenesis involving neurodevelopmental abnormalities, neurotransmitter disorders, and immune dysfunction. Up to 60% of cases do not respond adequately to medication, requiring innovative research strategies that will make recovery a realizable goal in schizophrenia rehabilitation. In this study, we focused on finding potential biological correlates that may predict the response to Cognitive Behavioral Therapy for psychosis (CBTp), specifically the brain-derived neurotrophic factor (BDNF), as well as cortisol and interleukin 1β (IL-1β) peripheral levels. Aims: i) Examine the therapeutic/clinical improvement under CBTp in principal and the possible efficacy of befriending pre-CBTp. ii) Assess psychosocial changes associated with therapeutic improvement under CBTp. iii) Assess changes in BDNF, cortisol, and IL-1β peripheral levels at different points of intervention and follow-ups and their possible correlations with the clinical and functional improvement. Methods: Thirty-two participants with schizophrenia received 4 weekly befriending sessions, then they were randomly assigned to two matched by age and gender groups of 16 participants: intervention group - undergoing 16 weekly sessions of CBT and waitlisted/control group. Biological samples were collected at baseline, pre-, during and post intervention, end of therapy as well as at the two follow-up points. Psychosocial outcomes were also measured at the same points. Results: We observed an improvement in the severity of positive, negative, and general pathology symptoms in participants following our intervention protocol, compared to the control group (as measured by PANSS, NSA-16 and CFS), an improvement in the level of functioning and quality of life (Q-LES-Q-SF, WHODAS 2.0, PSP) changes of peripheral levels of BDNF (not significant), IL-1b (decreasing inflammatory trend, but not significant) and a significant increase in awakening cortisol levels at the end of intervention. Conclusions: To our knowledge, this is the first time befriending is performed before the CBTp intervention in people with schizophrenia, preparing participants for a structured intervention. We also explored the possibility of identifying clinical and biological markers of therapeutic response in participants undergoing CBTp, concomitant with their usual medication regimen to better personalize the clinical decisions and decrease the costs of care.
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    Incorporating a Stepped Care Approach into Electronic Cognitive Behavioural Therapy for Depression: A Randomized Controlled Trial
    Jagayat, Jasleen K.; Neuroscience Studies; Alavi, Nazanin
    Depression is a leading cause of disability, annually affecting up to 300 million people worldwide, yet fewer than one third of patients receive care. Electronic cognitive behavioural therapy (e-CBT) is an effective treatment for depression. A stepped care model is a care model that begins treatment with the least resource intensive, yet effective, method while adapting care based on patients’ needs. This study investigated the efficacy of a stepped care e-CBT model for depression through the reduction of depressive symptoms. We hypothesized that the stepped care group will outperform the e-CBT only group. Participants were randomized to either the e-CBT only group (n = 28) or the e-CBT with stepped care group (n = 28). Both groups received a 13-weeks e-CBT program tailored to depression through a secure, online mental health platform called the Online Psychotherapy Tool (OPTT). Participants in the stepped care group received additional interventions based on their standard questionnaire scores and textual data. From lowest to highest intensity, the interventions included messages, phone calls, video calls, or a video call with a psychiatrist. For this study, 56 participants were recruited to complete an e-CBT only program (mean age = 38.9, 26.9% male) or e-CBT with stepped care program (mean age = 40.6, 42.4% male). The e-CBT program was effective in significantly reducing depressive symptoms; however, there were no significant differences in the reduction of depressive symptoms between the two groups. Although there were no significant differences observed between the number of participants who completed the program between groups, participants in the stepped care group, on average, took part in two more sessions than those who prematurely terminated participation in the e-CBT only group. Implementing a stepped care approach into e-CBT is an effective treatment for depression and the stepped care model can assist patients to complete more sessions in their treatment.
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    Incidence, Phenotype and Course of Acute Onset Restless Legs Syndrome (+ 4 Weeks) In Patients With Acute Stroke – Prospective Observational Cohort Study
    Makwana, Aditii N.; Neuroscience Studies; Shukla, Garima
    Objectives: The objective of this study was to determine prevalence of acute (new) onset restless legs syndrome (RLS) and of chronic bilateral symmetrical RLS in patients with recent stroke and evaluate the relationship with cardiocerebrovascular parameters like history of hypertension, subcortical location of stroke and cerebral small vessel disease. Methods: Consecutive acute stroke patients were recruited from the stroke unit of the Kingston Health Sciences Centre; total of 113 patients were included in the study. A pre-determined sleep questionnaire was administered, and details of stroke and hematology were collected from the hospital database for analysis. RLS diagnosis was done according to the criteria determined by the International Restless Legs Syndrome Study Group (IRLSSG). Results: Out of 113 patients, 30 patients (26%) met the IRLSSG criteria and were diagnosed with RLS, the majority of them being women. RLS diagnosis showed a statistically significant association with subcortical stroke location and cerebral small vessel disease. Half of these patients showed similar or worsening RLS symptoms upon a three to six month follow up. Conclusion: RLS prevalence in the stroke population has consistently been shown to be associated with subcortical stroke regions, highlighting its capability as a predictive factor for stroke and vice versa. Patients that develop acute RLS or other sleep disorders can experience symptoms for months post-stroke; therefore, detailed diagnostic and therapeutic interventions would be helpful in stroke recovery.
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    Synchronization and Inhibition of Saccade Action associated with Neurotypical Development and Psychiatric Disease
    Calancie, Olivia; Neuroscience Studies; Munoz, Doug; Khalid-Khan, Sarosh; Booij, Linda
    Humans execute approximately 200,000 saccades daily, representing swift conjugate eye movements necessary to align areas of interest with the fovea. Despite their apparent simplicity, the neural mechanisms signaling saccadic execution are intricate, spanning multiple brain regions. Consequently, saccades serve as a valuable proxy for assessing brain function and can unveil alterations stemming from physiological and pathological factors such as maturation, aging, trauma, or disease. In Chapter 2 of this study, I explore the connection between alternating bilateral saccades in response to rhythmic visual cues and therapeutic outcomes in Eye Movement Desensitization and Reprocessing (EMDR), a widely utilized treatment for post-traumatic stress disorder (PTSD). I theorize that the eye movements employed in EMDR coincide with the activation of the default mode network, a neural circuit associated with relaxation and memory reprocessing, which likely contributes to clinical recovery. In Chapter 3 I establish that this form of saccadic synchronization reaches an adult-like level of proficiency by middle adolescence. Additionally, I observe that alternating saccades at a fixed rate correspond to a consistent blink pattern and autonomic relaxation, as evidenced by reduced pupil size. In Chapter 4, I assess motor synchronization in individuals with borderline personality disorder (BPD) both with and without a comorbid diagnosis of attention-deficit hyperactivity disorder (ADHD). My findings support the preservation of motor synchronization in these disorders. However, I note irregularities in saccades toward randomly timed targets, indicative of heightened anticipation of forthcoming visual stimuli. I also reveal disparities in blink and pupil responses between individuals with BPD and matched controls, possibly a consequence of dysregulated dopamine signaling. In Chapter 5, I investigate oculomotor impulsivity across different phases of the anti-saccade task within BPD and ADHD/BPD groups. My results demonstrate that while BPD and ADHD/BPD groups exhibit analogous behavior at the onset of the anti-saccade trial (i.e. delayed visual fixation), individuals with ADHD/BPD display an additional impairment characterized by reduced preparation for the task, leading to an increased frequency of directional errors with short latencies. This dissertation enriches the existing oculomotor literature by describing saccadic motor synchronization and inhibition in typical neurodevelopment and in psychiatric disease.