Deep brain stimulation of the "medial forebrain bundle": sustained efficacy of antidepressant effect over years.

Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB) has emerged as a quite efficacious therapy for treatment resistant depression (TRD), leading to rapid antidepressant effects. In this study, we complete our assessment of our first 10 enrolled patients throughout one year post-implantation, showing sustained antidepressant effect up to 5 years. The primary outcome measure was a 50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score, which was interpreted as a response. Deterministic fiber tracking was used to individually map the target area. An insertional effect was seen during the 4-week sham stimulation phase (29% mean MADRS reduction, p = 0.02). However, after 2 weeks of initiating stimulation, five patients met response criteria (47% mean MADRS reduction, p < 0.001). One patient withdrew from study participation at 6 weeks. Twelve weeks after initiating stimulation, six of nine remaining patients had a >50% decrease in MADRS scores relative to baseline (52% mean MADRS reduction, p = 0.001); these same six patients continued to meet response criteria at 52 weeks (63% overall mean MADRS reduction, p < 0.001). Four of five patients who achieved the 5-year time point analysis continued to be responders (81% mean MADRS reduction, p < 0.001). Evaluation of modulated fiber tracts reveals significant common prefrontal/orbitofrontal connectivity to the target region in all responders. Key points learned from this study that we can incorporate in future protocols to better elucidate the effect of this therapy are a longer blinded sham stimulation phase and use of scheduled discontinuation concomitant with functional imaging.

A longitudinal study on deep brain stimulation of the medial forebrain bundle for treatment-resistant depression.

Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB) has been reported to lead to rapid antidepressant effects. In this longitudinal study, we expand upon the initial results we reported at 26 weeks (Fenoy et al., 2016), showing sustained antidepressant effects of MFB DBS on six patients with treatment-resistant depression (TRD) over 1 year. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary assessment tool. Deterministic fiber tracking was used to individually map the target area; analysis was performed to compare modulated fiber tracts between patients. Intraoperatively, upon stimulation at target, responders reported immediate increases in energy and motivation. An insertional effect was seen during the 4-week sham stimulation phase from baseline (28% mean MADRS reduction, p = 0.02). However, after 1 week of initiating stimulation, three of six patients had a > 50% decrease in MADRS scores relative to baseline (43% mean MADRS reduction, p = 0.005). One patient withdrew from study participation. At 52 weeks, four of remaining five patients have > 70% decrease in MADRS scores relative to baseline (73% mean MADRS reduction, p = 0.007). Evaluation of modulated fiber tracts reveals significant common orbitofrontal connectivity to the target region in all responders. Neuropsychological testing and 18F-fluoro-deoxyglucose-positron emission tomography cerebral metabolism evaluations performed at baseline and at 52 weeks showed minimal changes and verified safety. This longitudinal evaluation of MFB DBS demonstrated rapid antidepressant effects, as initially reported by Schlaepfer et al. (2013), and supports the use of DBS for TRD.

Looking at the sunny side of life: age-related change in an event-related potential measure of the negativity bias.

Studies of the negativity bias have demonstrated that negative information has a stronger influence than positive information in a wide range of cognitive domains. At odds with this literature is extensive work now documenting emotional and motivational shifts that result in a positivity effect in older adults. It remains unclear, however, whether this age-related positivity effect results from increases in processing of positive information or from decreases in processing of negative information. Also unknown is the specific time course of development from a negative bias to an apparently positive one. The present study was designed to investigate the negativity bias across the life span using an event-related potential measure of responding to emotionally valenced images. The results suggest that neural reactivity to negative images declines linearly with age, but responding to positive images is surprisingly age invariant across most of the adult life span.

Rotation rate and duration effects on the somatogyral illusion.

INTRODUCTION: Aviation spatial disorientation mishaps remain a concern, especially due to their fatality rate. Some of the most insidious disorientations are due to vestibular stimuli in the absence of visual cues. A category of such disorientations are known as somatogyral illusions. METHODS: To determine the effects of spin rate and duration on the perception of the somatogyral illusion, we examined the subjective response of pilots and non-pilots to rotation around the yaw axis in a flight simulator in a manner that would mimic two vestibular illusions found in flight: the washout of the semi-circular canals following sustained turns, and the illusory counter-rotation following return to straight and level flight. There were 29 subjects (14 pilots) who were seated blindfolded in a flight simulator which accelerated to constant plateau rotation rates of 20, 70, and 120 degrees x s(-1) and then decelerated to stationary; plateaus were 10, 20, or 40 s. Subjects reported 1) the time when the perception of rotation ceased (i.e., the subjective time until washout was reached); 2) the relative magnitude of the counter-rotation experienced; and 3) the time until the perception of counter-rotation ceased. Subjects also manipulated a slider to provide a continuous subjective measure of their experience of rotation. RESULTS: The two time measures increased with increases in both the duration and magnitude of the spin. The increase in perceived washout time with spin rate was non-linear (geometric). There was an interaction between spin duration and spin rate on the experience of illusory counter-rotation magnitude such that at low rates, spin duration had no effect, but its effect increased at faster rates. The time constant of adaptation of the semicircular canals was estimated to be 8.3 s. DISCUSSION: The effects were validated against a model of semicircular canal and cupola adaptation, which predicted the data with high accuracy. Pilots and non-pilots did not differ in their illusory experience.