Browsing by Author "Ramasubbu, Rajamannar"

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    A Preliminary Study of the Influence of Age of Onset and Childhood Trauma on Cortical Thickness in Major Depressive Disorder
    (2014-03-06) Jaworska, Natalia; MacMaster, Frank P.; Gaxiola, Ismael; Cortese, Filomeno; Goodyear, Bradley; Ramasubbu, Rajamannar
    Background. Major depressive disorder (MDD) neural underpinnings may differ based on onset age and childhood trauma. We assessed cortical thickness in patients who differed in age of MDD onset and examined trauma history influence. Methods. Adults with MDD () and controls (HC; ) underwent magnetic resonance imaging. Twenty patients had MDD onset 24 years of age (pediatric onset) and 16 had onset 25 years of age (adult onset). The MDD group was also subdivided into those with () and without () physical and/or sexual abuse as assessed by the Childhood Trauma Questionnaire (CTQ). Cortical thickness was analyzed with FreeSurfer software. Results. Thicker frontal pole and a tendency for thinner transverse temporal cortices existed in MDD. The former was driven by the pediatric onset group and abuse history (independently), particularly in the right frontal pole. Inverse correlations existed between CTQ scores and frontal pole cortex thickness. A similar inverse relation existed with left inferior and right superior parietal cortex thickness. The superior temporal cortex tended to be thinner in pediatric versus adult onset groups with childhood abuse. Conclusions. This preliminary work suggests neural differences between pediatric and adult MDD onset. Trauma history also contributes to cytoarchitectural modulation. Thickened frontal pole cortices as a compensatory mechanism in MDD warrant evaluation.
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    Dosing of Electrical Parameters in Deep Brain Stimulation (DBS) for Intractable Depression: A Review of Clinical Studies
    (2018-07-11) Ramasubbu, Rajamannar; Lang, Stefan; Kiss, Zelma H. T.; lan
    Background: The electrical parameters used for deep brain stimulation (DBS) in movement disorders have been relatively well studied, however for the newer indications of DBS for psychiatric indications these are less clear. Based on the movement disorder literature, use of the correct stimulation parameters should be crucial for clinical outcomes. This review examines the stimulation parameters used in DBS studies for treatment resistant depression (TRD) and their relevance to clinical outcome and brain targets. Methods: We examined the published studies on DBS for TRD archived in major databases. Data on stimulus parameters (frequency, pulse width, amplitude), stimulation mode, brain target, efficacy, safety, and duration of follow up were extracted from 29 observational studies including case reports of patients with treatment resistant unipolar, bipolar, and co-morbid depression. Results: The algorithms commonly used to optimize efficacy were increasing amplitude followed by changing the electric contacts or increasing pulse width. High frequency stimulation (>100 Hz) was applied in most cases across brain targets. Keeping the high frequency stimulation constant, three different combinations of parameters were mainly used: (i) short pulse width (60-90 us) and low amplitude (0-4 V), (ii) short pulse width and high amplitude (5-10 V), (iii) long pulse width (120-450 us) and low amplitude. There were individual variations in clinical response to electrical dosing and also in the time of clinical recovery. There was no significant difference in mean stimulation parameters between responders and non-responders suggesting a role for stimulation unrelated factors in response. Conclusions: Although limited by open trials and small sample size, three optimal stimulation parameter combinations emerged from this review. Studies are needed to assess the comparative efficacy and safety of these combinations, such as a registry of data from patients undergoing DBS for TRD with individual data on stimulation parameters.
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    Dosing of Electrical Parameters in Deep Brain Stimulation (DBS) for Intractable Depression: A Review of Clinical Studies
    (Frontiers, 2018-01) Ramasubbu, Rajamannar; Lang, Stefan; Kiss, Zelma H. T.
    Background: The electrical parameters used for deep brain stimulation (DBS) in movement disorders have been relatively well studied, however for the newer indications of DBS for psychiatric indications these are less clear. Based on the movement disorder literature, use of the correct stimulation parameters should be crucial for clinical outcomes. This review examines the stimulation parameters used in DBS studies for treatment resistant depression (TRD) and their relevance to clinical outcome and brain targets. Methods: We examined the published studies on DBS for TRD archived in major databases. Data on stimulus parameters (frequency, pulse width, amplitude), stimulation mode, brain target, efficacy, safety, and duration of follow up were extracted from 29 observational studies including case reports of patients with treatment resistant unipolar, bipolar, and co-morbid depression. Results: The algorithms commonly used to optimize efficacy were increasing amplitude followed by changing the electric contacts or increasing pulse width. High frequency stimulation (>100 Hz) was applied in most cases across brain targets. Keeping the high frequency stimulation constant, three different combinations of parameters were mainly used: (i) short pulse width (60-90 us) and low amplitude (0-4 V), (ii) short pulse width and high amplitude (5-10 V), (iii) long pulse width (120-450 us) and low amplitude. There were individual variations in clinical response to electrical dosing and also in the time of clinical recovery. There was no significant difference in mean stimulation parameters between responders and non-responders suggesting a role for stimulation unrelated factors in response. Conclusions: Although limited by open trials and small sample size, three optimal stimulation parameter combinations emerged from this review. Studies are needed to assess the comparative efficacy and safety of these combinations, such as a registry of data from patients undergoing DBS for TRD with individual data on stimulation parameters.
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    On the Malleability of Human Cognition: Working Memory Training and Transfer
    (2017) Clark, Cameron; Goghari, Vina; Campbell, Tavis; Longman, Richard Stewart; Goodyear, Bradley; Ramasubbu, Rajamannar; Yang, Lixia
    Training working memory (WM) to increase WM capacity and fluid intelligence (Gf) has received much experimental attention in recent years, though its efficacy remains highly controversial. The current study investigated the effect of a randomized six-week online WM intervention on cognitive abilities and patterns of neural activation in a community-recruited sample of healthy young adults, in relation to both a processing speed training active control condition, as well as a no-contact control condition. Results of this randomized trial are discussed in three parts: Chapter 2 examines group-level fMRI activation patterns for tasks of WM and Gf before the training intervention. Consistent with previous research, results indicate large areas of fronto-parietal activation in response to increasing task demands for our WM task, which largely subsume more circumscribed regions of activation for our Gf task. These results are discussed in terms of a task-general central network which may underlie performance of WM, Gf, and perhaps even goal-directed behaviour more generally. Chapter 3 investigates potential differences in a wide range of cognitive test scores before and after WM training, processing speed training, or no-contact. Results revealed support for the null hypothesis across all cognitive tests administered. Because these results are consistent with experimental trials of equal or greater methodological rigor, we suggest that future research re-focus on promising interventions known to increase memory performance in healthy young adults; and/or examine alternative populations in which WM training may be efficacious. Chapter 4 examines potential differences in pre- and post-training patterns of neural activation for WM and Gf tasks in our WM training, and processing speed training groups. Results indicated significant post-training reductions in activation for the WM trained group in relation to the processing speed group for the WM task, but not the Gf task. These results suggest that WM training does not affect patterns of neural activation for Gf tasks. We suggest that future research investigate neural correlates of WM training in populations for which WM itself is impaired; and/or WM training interventions in populations that have returned more promising results compared to those with healthy young adults.