Effect of 3-Day and 21-Day Hypoxic Preconditioning on Recovery Following Cerebral Ischemia in Rats.

We have previously reported that in a rat model of chronic hypoxia, HIF-1α and its target genes have significantly accumulated by 3 days of exposure, whereas no significant increase in capillary density has occurred; there is a significant increase in capillary density at 21 days of chronic hypoxic exposure. In this study we hypothesize that by utilizing 3 days and 21 days of hypoxic preconditioning, we would distinguish between the relative neuroprotective contributions of the accumulation of HIF-1α and its target genes and angiogenic adaptation in a rat middle cerebral artery occlusion (MCAO) model. Rats were randomly assigned to either hypoxic precondition groups (3-day and 21-day hypoxia) or normoxic control group. Hypoxic animals were kept in a hypobaric chamber at a constant pressure of 0.5 atmosphere (380 mmHg, equivalent to 10% normobaric oxygen at sea level) for either 3 or 21 days. Normoxic controls were housed in the same room next to the hypobaric chamber. Erythropoietin (EPO) was measured at 3 and 21 days of hypoxia using Western blotting analysis. Infarct volumes were measured following 24 hours of permanent MCAO. We found that EPO is upregulated at 3 days of hypoxia and returns to baseline by 21 days of hypoxia. The infarct volumes following 24-hour MCAO were significantly reduced with 3-day hypoxic preconditioning when compared to normoxic controls (%, 31.8 ± 5, n = 9 vs. 50.1 ± 10.9, n = 7). No significant differences in infarct volume were seen between the normoxic controls and 21-day hypoxic preconditioned rats. We have shown that a 3-day hypoxic preconditioning, but not 21-day hypoxic preconditioning, provides significant neuroprotection against focal ischemia in rats, supporting a larger role for the accumulations of HIF-1α and upregulation of its target genes in the neuroprotection against focal ischemia.

Mechanisms that allow cortical preparatory activity without inappropriate movement.

We reveal a novel mechanism that explains how preparatory activity can evolve in motor-related cortical areas without prematurely inducing movement. The smooth eye movement region of the frontal eye fields (FEFSEM) is a critical node in the neural circuit controlling smooth pursuit eye movement. Preparatory activity evolves in the monkey FEFSEM during fixation in parallel with an objective measure of visual-motor gain. We propose that the use of FEFSEM output as a gain signal rather than a movement command allows for preparation to progress in pursuit without causing movement. We also show that preparatory modulation of firing rate in FEFSEM predicts movement, providing evidence against the 'movement-null' space hypothesis as an explanation of how preparatory activity can progress without movement. Finally, there is a partial reorganization of FEFSEM population activity between preparation and movement that would allow for a directionally non-specific component of preparatory visual-motor gain enhancement in pursuit.

The Neural Basis for Response Latency in a Sensory-Motor Behavior.

We seek a neural circuit explanation for sensory-motor reaction times. In the smooth eye movement region of the frontal eye fields (FEFSEM), the latencies of pairs of neurons show trial-by-trial correlations that cause trial-by-trial correlations in neural and behavioral latency. These correlations can account for two-third of the observed variation in behavioral latency. The amplitude of preparatory activity also could contribute, but the responses of many FEFSEM neurons fail to support predictions of the traditional "ramp-to-threshold" model. As a correlate of neural processing that determines reaction time, the local field potential in FEFSEM includes a brief wave in the 5-15-Hz frequency range that precedes pursuit initiation and whose phase is correlated with the latency of pursuit in individual trials. We suggest that the latency of the incoming visual motion signals combines with the state of preparatory activity to determine the latency of the transient response that controls eye movement. IMPACT STATEMENT: The motor cortex for smooth pursuit eye movements contributes to sensory-motor reaction time through the amplitude of preparatory activity and the latency of transient, visually driven responses.

Neural implementation of Bayesian inference in a sensorimotor behavior.

Actions are guided by a Bayesian-like interaction between priors based on experience and current sensory evidence. Here we unveil a complete neural implementation of Bayesian-like behavior, including adaptation of a prior. We recorded the spiking of single neurons in the smooth eye-movement region of the frontal eye fields (FEFSEM), a region that is causally involved in smooth-pursuit eye movements. Monkeys tracked moving targets in contexts that set different priors for target speed. Before the onset of target motion, preparatory activity encodes and adapts in parallel with the behavioral adaptation of the prior. During the initiation of pursuit, FEFSEM output encodes a maximum a posteriori estimate of target speed based on a reliability-weighted combination of the prior and sensory evidence. FEFSEM responses during pursuit are sufficient both to adapt a prior that may be stored in FEFSEM and, through known downstream pathways, to cause Bayesian-like behavior in pursuit.

Control of the strength of visual-motor transmission as the mechanism of rapid adaptation of priors for Bayesian inference in smooth pursuit eye movements.

Bayesian inference provides a cogent account of how the brain combines sensory information with "priors" based on past experience to guide many behaviors, including smooth pursuit eye movements. We now demonstrate very rapid adaptation of the pursuit system's priors for target direction and speed. We go on to leverage that adaptation to outline possible neural mechanisms that could cause pursuit to show features consistent with Bayesian inference. Adaptation of the prior causes changes in the eye speed and direction at the initiation of pursuit. The adaptation appears after a single trial and accumulates over repeated exposure to a given history of target speeds and directions. The influence of the priors depends on the reliability of visual motion signals: priors are more effective against the visual motion signals provided by low-contrast vs. high-contrast targets. Adaptation of the direction prior generalizes to eye speed and vice versa, suggesting that both priors could be controlled by a single neural mechanism. We conclude that the pursuit system can learn the statistics of visual motion rapidly and use those statistics to guide future behavior. Furthermore, a model that adjusts the gain of visual-motor transmission predicts the effects of recent experience on pursuit direction and speed, as well as the specifics of the generalization between the priors for speed and direction. We suggest that Bayesian inference in pursuit behavior is implemented by distinctly non-Bayesian internal mechanisms that use the smooth eye movement region of the frontal eye fields to control of the gain of visual-motor transmission.NEW & NOTEWORTHY Bayesian inference can account for the interaction between sensory data and past experience in many behaviors. Here, we show, using smooth pursuit eye movements, that the priors based on past experience can be adapted over a very short time frame. We also show that a single model based on direction-specific adaptation of the strength of visual-motor transmission can explain the implementation and adaptation of priors for both target direction and target speed.

A prospective, multi-institutional comparative effectiveness study of lumbar spine surgery in morbidly obese patients: does minimally invasive transforaminal lumbar interbody fusion result in superior outcomes?

BACKGROUND: Obese and morbidly obese patients undergoing lumbar spinal fusion surgery are a challenge to the operating surgeon. Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and open-TLIF have been performed for many years with good results; however, functional outcomes after lumbar spine surgery in this subgroup of patients remain poorly understood. Furthermore, whether index MIS-TLIF or open-TLIF for the treatment of degenerative disc disease or spondylolisthesis in morbidly obese results in superior postoperative functional outcomes remains unknown. METHODS: A total of 148 (MIS-TLIF: n = 40, open-TLIF: n = 108) obese and morbidly obese patients undergoing index lumbar arthrodesis for low back pain and/or radiculopathy between January 2003 and December 2010 were selected from a multi-institutional prospective data registry. We collected and analyzed data on patient demographics, postoperative complications, back pain, leg pain, and functional disability over 2 years. Patients completed the Oswestry Disability Index (ODI), Medical Outcomes Study Short-Form 36 (SF-36), and back and leg pain numerical rating scores before surgery and then at 12 and 24 months after surgery. Clinical outcomes and complication rates were compared between both patient cohorts. RESULTS: Compared with preoperative status, Visual Analog Scale (VAS) back and leg pain, ODI, and SF-36 physical component score/mental component score were improved in both groups. Both MIS-TLIF and open-TLIF patients showed similar 2-year improvement in VAS for back pain (MIS-TLIF: 2.42 ± 3.81 vs. open-TLIF: 2.33 ± 3.67, P = 0.89), VAS for leg pain (MIS-TLIF: 3.77 ± 4.53 vs. open-TLIF: 2.67 ± 4.10, P = 0.18), ODI (MIS-TLIF: 11.61 ± 25.52 vs. open-TLIF: 14.88 ± 22.07, P = 0.47), and SF-36 physical component score (MIS-TLIF: 8.61 ± 17.72 vs. open-TLIF: 7.61 ± 15.55, P = 0.93), and SF-36 mental component score (MIS-TLIF: 4.35 ± 22.71 vs. open-TLIF: 5.96 ± 21.09, P = 0.69). Postoperative complications rates between both cohorts were also not significantly divergent between (12.50% vs. 11.11%, P = 0.51). CONCLUSION: MIS-TLIF is a safe and viable option for lumbar fusion in morbidly obese patients and, compared with open-TLIF, resulted in similar improvement in pain and functional disability. Postoperative complications rates between both cohorts were also not significantly divergent.

No difference in postoperative complications, pain, and functional outcomes up to 2 years after incidental durotomy in lumbar spinal fusion: a prospective, multi-institutional, propensity-matched analysis of 1,741 patients.

BACKGROUND: Incidental durotomies occur in up to 17% of spinal operations. Controversy exists regarding the short- and long-term consequences of durotomies. PURPOSE: The primary aim of this study was to assess the effect of incidental durotomies on the immediate postoperative complications and patient-reported outcome measures. STUDY DESIGN: Prospective study. PATIENT SAMPLE: A total of 1,741 patients undergoing index lumbar spine fusion were selected from a multi-institutional prospective data registry. OUTCOME MEASURES: Patient-reported outcome measures used in this study included back pain (BP-Visual Analog Scale), leg pain (LP-Visual Analog Scale), and Oswestry Disability Index. METHODS: A total of 1,741 patients were selected from a multi-institutional prospective data registry, who underwent primary lumbar fusion for low back pain and/or radiculopathy between January 2003 and December 2010. We collected and analyzed data on patient demographics, postoperative complications, back pain, leg pain, and functional disability over 2 years, with risk-adjusted propensity score modeling. RESULTS: Incidental durotomies occurred in 70 patients (4%). Compared with the control group (n=1,671), there was no significant difference in postoperative infection (p=.32), need for reoperation (p=.85), or symptomatic neurologic damage (p=.66). At 1- and 2-year follow-up, there was no difference in patient-reported outcomes of back pain (BP-Visual Analog Scale), leg pain (LP-Visual Analog Scale), or functional disability (Oswestry Disability Index) (p>.3), with results remaining consistent in the propensity-matched cohort analysis (p>.4). CONCLUSION: Within the context of an on-going debate on the consequences of incidental durotomy, we found no difference in neurologic symptoms, infection, reoperation, back pain, leg pain, or functional disability over a 2-year follow-up period.