1999 — 2003 |
Lisanby, Sarah H |
K08Activity Code Description: To provide the opportunity for promising medical scientists with demonstrated aptitude to develop into independent investigators, or for faculty members to pursue research aspects of categorical areas applicable to the awarding unit, and aid in filling the academic faculty gap in these shortage areas within health profession's institutions of the country. |
Neurobiology of Emotional Processes--Rtms Studies @ Columbia University Health Sciences
stimulus /response; emotions; neural information processing; magnetic field; brain electrical activity; prefrontal lobe /cortex; electrostimulus; brain mapping; behavioral /social science research tag; electrodes; human subject; positron emission tomography; Macaca mulatta; magnetic resonance imaging; volunteer;
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0.936 |
2009 — 2012 |
Lisanby, Sarah H Weiner, Richard D. |
U01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
2/8-Prolonging Remission in Depressed Elderly (Pride)
While advances have been made in the acute treatment of geriatric depression, failure to maintain remission following successful treatment remains a major public health problem. In particular, loss of antidepressant response can result in ongoing functional impairment and increased risk of suicide. This is especially salient for severe and/or treatment resistant illness, even after successful ECT. This competing continuation application builds upon our prior work demonstrating that continuation pharmacotherapy and continuation ECT were equally but only modestly effective over 6 months. These results highlight the need to develop improved strategies to maintain remission and optimize functional outcomes. The current application tests a novel strategy that utilizes pharmacotherapy-enhanced ECT in the acute phase. It then combines the 2 continuation modalities [pharmacotherapy and continuation ECT], and introduces a novel patient-focused individualization of the ECT schedule (Symptom-Titrated, Algorithm-Based Longitudinal ECT (STABLE)) to enhance long-term outcomes in late-life depression. In STABLE, the ECT schedule is clinically driven to prevent over-treatment of those who do not need it, and to permit re-capturing clinical response for those patients who might have otherwise relapsed with a rigid dosing schedule. STABLE combines a fixed ECT taper followed by an individualized, flexible ECT schedule responsive to symptom re-emergence. This approach provides the first operationalized guidance to the field regarding how to conduct continuation ECT. The primary aim of the Prolonging Remission In Depressed Elderly (PRIDE) trial is to compare, in a randomized clinical trial of patients with late-life depression, the relative efficacy, functional outcomes, and tolerability of two strategies to sustain antidepressant effect after successful acute treatment: 1) combination pharmacotherapy with venlafaxine and lithium (PHARM) and 2) the same combination of pharmacotherapy plus symptom-titrated ECT (STABLE). At 7 sites, 322 patients receive an acute course of ECT augmented by standardized medication (Phase 1); 188 remitters are randomly assigned to one of the 2 groups and followed for 6 months (Phase 2). The primary outcome measure is the longitudinal continuous Hamilton Rating Scale for Depression (HRSD-24). Secondary outcomes are measures of function and tolerability validated in the geriatric sample.
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0.936 |
2010 — 2014 |
Lisanby, Sarah H Peterchev, Angel V (co-PI) [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Rational Dosing For Electric and Magnetic Seizure Therapy
DESCRIPTION (provided by applicant): This translational project will develop a novel framework to optimize the dosing of seizure therapies for the treatment of medication resistant disorders. Despite advances in antidepressant interventions, none has replaced electroconvulsive therapy (ECT) in its acute efficacy and spectrum of action. However, ECT carries the risk of significant cognitive side effects, some of which are lasting. Major improvements in the risk/benefit ratio of ECT have been made over the past few decades, including the introduction of more focal stimulation with magnetic seizure therapy (MST), yet our knowledge of the optimal dosing of seizure therapies remains relatively rudimentary. Lacking an understanding of the biophysical and physiological mechanisms, refinements in ECT/MST technique must rely exclusively on time-consuming and costly clinical trials. Consequently, key questions remain unanswered, such as: (1) how to position the electrode or coil to TARGET stimulation to specific brain areas, (2) how best to INDIVIDUALIZE the dosage for each patient, and (3) how to OPTIMIZE stimulus parameters for efficient seizure induction. Answers to these questions could lead to substantial advances in the tolerability of the treatment and would inform clinical decision-making. Addressing this knowledge gap, we propose a new platform for the rational dosing of electric and magnetic seizure therapy that couples computational modeling with empirical validation to inform the targeting, individualization, and optimization of ECT/MST technique. This 5-year collaborative project spanning the disciplines of engineering and psychiatry entails two interrelated lines of work: computational modeling, and in vivo testing to physiologically calibrate the model and empirically determine the dynamic interaction between pulse train characteristics and seizure initiation. This proposal has 3 aims: (AIM 1) to inform TARGETING, we will simulate the strength and focality of neural stimulation as a function of ECT electrode and MST coil configuration using realistic head models calibrated through empirical neural threshold measurement in vivo;(AIM 2) to guide the INDIVIDUALIZATION of dosage, we will titrate pulse amplitude for efficient seizure induction in vivo and evaluate it as a means of controlling the focality of stimulation;and (AIM 3) to OPTIMIZE train parameters, we will empirically determine the most efficient frequency and directionality of pulse trains for seizure induction. This approach accounts for tissue conductivity and the anisotropy of white matter as measured by diffusion tensor imaging, it includes physiological calibration of field maps relative to neural activation thresholds, and it evaluates relatively ignored parameters which are central to controlling the focality and physiological action of seizure therapies. Pilot data supporting each of the aims demonstrate that lowering pulse amplitude improves focality and seizure induction is more efficient with lower frequencies and unidirectional pulse trains. This work provides a basis for rational dosing of seizure therapies that could help improve their risk/benefit ratio and guide the development of safer alternatives for severely ill patients. PUBLIC HEALTH RELEVANCE: Clinical depression affects upwards of 34 million US citizens, but only about one third of those are effectively treated with medications. For the remainder, electroconvulsive therapy (ECT) is an effective option but it carries a risk of side effects. This project couples state-of-the-art engineering methods with the latest developments in clinical psychiatry to inform the dosing of existing and novel seizure therapies so that persons with severe depression and other disabling disorders will have more effective and safer treatment options.
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0.906 |