Biology subjects

Stimpson, K. H.

Publications and source records attributed to Stimpson, K. H..

3 recordsLinked to original sources

bioRxiv2019

Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) Induces Functional Connectivity Changes in Emotion Regulation Brain Areas for MDD Patients

BackgroundMajor depressive disorder (MDD) is prevalent and debilitating, and development of improved treatments is limited in part by insufficient understanding of the mechanism of disease remission. In turn, efforts to elucidate mechanisms have been challenging due to disease heterogeneity and limited effectiveness of treatments, which require weeks-to-months to induce remission. We recently developed a form of repetitive transcranial magnetic stimulation that induces remission in 90% of individuals with severe, treatment resistant MDD in 1-5 days (SAINT). This provides a new tool to begin exploring the network-level mechanisms of MDD remission. ObjectiveDetermine the functional connectivity (fc) changes that occur with SAINT in brain regions associated with emotion regulation. MethodsResting-state fMRI scans were performed just prior to (baseline), and following, open-label SAINT in 18 participants with severe, treatment-resistant MDD. Fc was determined between regions of interest (ROIs) defined a priori with well-described roles in emotion regulation. ResultsFollowing SAINT treatment fc was significantly decreased between the following ROI pairs: dorsolateral prefrontal cortex (DLPFC)-striatum, DLPFC-amygdala, default mode network (DMN)-subgenual cingulate cortex (sgACC), DMN-amygdala, DMN-striatum, amygdala-striatum, and between amygdala subregions. Greater clinical improvements were associated with larger decreases in fc between DLPFC-amygdala and DLPFC-insula. Greater clinical improvements were associated with smaller decreases in fc between sgACC-DMN. Significant increases and decreases in fc between insula-amygdala were observed depending on the subregions. Greater clinical improvements were associated with lower baseline fc between DMN-DLPFC, DMN-striatum, and DMN-ventrolateral prefrontal cortex. ConclusionSAINT-induced remission from depression is associated with fc changes that suggest improved regulation of emotion. Although preliminary, this leads us to hypothesize that interventions that augment top-down regulation of emotion may be effective depression treatments.

clinical trials↗

bioRxiv2019

Application of a novel force-field to manipulate the relationship between pelvis motion and step width in human walking

Motion of the pelvis throughout a step predicts step width during human walking. This behavior is often considered an important component of ensuring bipedal stability, but can be disrupted in populations with neurological injuries. The purpose of this study was to determine whether a novel force-field that exerts mediolateral forces on the legs can manipulate the relationship between pelvis motion and step width, providing proof-of-concept for a future clinical intervention. We designed a force-field able to: 1) minimize the delivered mediolateral forces (Transparent mode); 2) apply mediolateral forces to assist the leg toward mechanically-appropriate step widths (Assistive mode); and 3) apply mediolateral forces to perturb the leg away from mechanically-appropriate step widths (Perturbing mode). Neurologically-intact participants were randomly assigned to either the Assistive group (n=12) or Perturbing group (n=12), and performed a series of walking trials in which they interfaced with the force-field. We quantified the step-by-step relationship between mediolateral pelvis displacement and step width using partial correlations. Walking in the Transparent force-field had a minimal effect on this relationship. However, force-field assistance directly strengthened the relationship between pelvis displacement and step width, whereas force-field perturbations weakened this relationship. Both assistance and perturbations were followed by short-lived effects during a wash-out period, in which the relationship between pelvis displacement and step width differed from the baseline value. The present results demonstrate that the link between pelvis motion and step width can be manipulated through mechanical means, which may be useful for retraining gait balance in clinical populations.

bioengineering↗

bioRxiv2019

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD).

BackgroundCurrent treatments for depression are limited by suboptimal efficacy, delayed response, and frequent side effects. Intermittent theta-burst stimulation (iTBS) is a non-invasive brain stimulation treatment that is FDA-approved for treatment-resistant depression (TRD). Recent methodological advancements suggest iTBS could be improved through 1) treating with multiple sessions per day at optimally-spaced intervals, 2) applying a higher overall pulse-dose of stimulation and 3) precision targeting of the left dorsolateral prefrontal cortex (L-DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. We examined the feasibility, tolerability, and preliminary efficacy of an accelerated, high-dose, resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for TRD termed Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT). MethodsTwenty-one participants with TRD received open-label SAINT. FcMRI was used to individually target the region of L-DLPFC most anticorrelated with sgACC. Fifty iTBS sessions (1800 pulses per session, 50-minute inter-session interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT. ResultsNineteen of 21 participants (90.48%) met criteria for remission ([≤]10 on the Montgomery-[A]sberg Depression Rating Scale) immediately after SAINT. Neuropsychological testing demonstrated no negative cognitive side-effects. There were no seizures or other severe adverse events. DiscussionOur accelerated, high-dose, iTBS protocol with fcMRI-guided targeting (SAINT) was well tolerated and safe. Efficacy was strikingly high, especially for this treatment-resistant population. Double-blinded sham-controlled trials are required to confirm the high remission rate found in this initial study. Trial registrationClinicalTrials.gov NCT03240692

clinical trials↗