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The superior temporal gyrus (STG) is on the inferior-lateral brain surface near the external ear. In macaques, 2/3 of the STG is occupied by an auditory cortical region, the "parabelt," which is part of a network of inferior temporal areas subserving communication and social cognition as well as object recognition and other functions. However, due to its location beneath the squamous temporal bone and temporalis muscle, the STG, like other inferior temporal regions, has been a challenging target for physiological studies in awake-behaving macaques. We designed a new procedure for implanting recording chambers to provide direct access to the STG, allowing us to evaluate neuronal properties and their topography across the full extent of the STG in awake-behaving macaques. Initial surveys of the STG have yielded several new findings. Unexpectedly, STG sites in monkeys that were listening passively responded to tones with magnitudes comparable to those of responses to 1/3 octave band-pass noise. Mapping results showed longer response latencies in more rostral sites and possible tonotopic patterns parallel to core and belt areas, suggesting the reversal of gradients between caudal and rostral parabelt areas. These results will help further exploration of parabelt areas.
Copyright © 2015 the authors 0270-6474/15/354140-11$15.00/0.
OBJECTIVE - The updated clinical practice guidelines for the management of pain, agitation, and delirium recommend either daily sedation interruption or maintaining light levels of sedation as methods to improve outcomes for patients who are sedated in the ICU. We review the evidence supporting both methods and discuss whether one method is preferable or if they should be used concurrently.
DATA SOURCE - Original research articles identified using the electronic PubMed database.
STUDY SELECTION AND DATA EXTRACTION - Randomized controlled trials and large prospective cohort studies of mechanically ventilated ICU patients requiring sedation were selected.
DATA SYNTHESIS - The methods of daily sedation interruption and targeting light sedation levels (including avoidance of deep sedation) are safe in critically ill patients with no increase, and a potential decrease, in long-term psychiatric disturbances. Randomized trials comparing these methods with standard care, which has traditionally involved moderate to heavy sedation, found that both methods reduced duration of mechanical ventilation and ICU length of stay. Additionally, one trial noted that daily sedation interruption paired with spontaneous breathing trials improved 1-year survival, whereas a large observational study found that deep sedation was associated with decreased 180-day survival. Two common characteristics of these interventions in trials showing benefits were avoidance of deep levels of sedation and significant reductions in sedative doses, especially benzodiazepines. Thus, combining targeted light sedation with daily sedation interruption may be more beneficial than either method alone if sedative doses are reduced and arousal and mobility are facilitated during the ICU stay.
CONCLUSION - Daily sedation interruption and targeting light sedation levels are safe and proven to improve outcomes for sedated ICU patients when these approaches result in reduced sedative exposure and facilitate arousal. It remains unclear as to whether one approach is superior, and further studies are needed to evaluate which patients benefit most from either or both techniques.
OBJECTIVES - Standard sleep scoring criteria may be unreliable when applied to critically ill patients. We sought to quantify typical and atypical polysomnographic findings in critically ill patients and to begin development and reliability testing of methodology to characterize the atypical polysomnographic tracings that confound standard sleep scoring criteria.
DESIGN - Prospective convenience sample.
SETTING - Two academic, tertiary care medical centers.
PATIENTS - Thirty-seven critically ill, mechanically ventilated, medical ICU patients.
INTERVENTIONS - None.
MEASUREMENTS AND MAIN RESULTS - Mechanically ventilated subjects were monitored by continuous polysomnography. After noting frequent atypical polysomnographic findings (i.e., lack of stage N2 markers, the presence of polymorphic delta, burst suppression, or isoelectric electroencephalography), attempts to use standard sleep scoring criteria alone were abandoned. Atypical polysomnographic findings were characterized and used to develop a modified scoring system. Polysomnographic data were scored manually via this revised scoring scheme. Of 37 medical ICU patients enrolled, 36 experienced atypical sleep, which accounted for 85% of all recorded data, with 5.1% normal sleep and 9.4% wake. Coupling observed patient arousal levels with polysomnographic characteristics revealed that standard polysomnographic staging criteria did not reliably determine the presence or absence of sleep. Rapid eye movement occurred in only five patients (14%). The revised scoring system incorporating frequently seen atypical characteristics yielded very high interrater reliability (weighted κ = 0.80; bootstrapped 95% CI, [0.48, 0.89]).
CONCLUSIONS - Analysis of polysomnographic data revealed profound deficiencies in standard scoring criteria due to a predominance of atypical polysomnographic findings in ventilated patients. The revised scoring scheme proved reliable in sleep staging and may serve as a building block in future work.
The laminar structure of the cortex has previously been explored both in non-human primates and human subjects using high-resolution functional magnetic resonance imaging (fMRI). However, whether the spatial specificity of the blood-oxygenation-level-dependent (BOLD) fMRI is sufficiently high to reveal lamina specific organization in the cortex reliably is still unclear. In this study we demonstrate for the first time the detection of such layer-specific activation in awake monkeys at the spatial resolution of 200 × 200 × 1000 μm(3) in a vertical 4.7 T scanner. Results collected in trained monkeys are high in contrast-to-noise ratio and low in motion artifacts. Isolation of laminar activation was aided by choosing the optimal slice orientation and thickness using a novel pial vein pattern analysis derived from optical imaging. We found that the percent change of GE-BOLD signal is the highest at a depth corresponding to layer IV. Changes in the middle layers (layer IV) were 30% greater than changes in the top layers (layers I-III), and 32% greater than the bottom layers (layers V/VI). The laminar distribution of BOLD signal correlates well with neural activity reported in the literature. Our results suggest that the high intrinsic spatial resolution of GE-BOLD signal is sufficient for mapping sub-millimeter functional structures in awake monkeys. This degree of spatial specificity will be useful for mapping both laminar activations and columnar structures in the cerebral cortex.
Copyright © 2012 Elsevier Inc. All rights reserved.
Brodmann divided the neocortex into 47 different cortical areas based on histological differences in laminar myeloarchitectonic and cytoarchitectonic defined structure. The ability to do so in vivo with anatomical magnetic resonance (MR) methods in awake subjects would be extremely advantageous for many functional studies. However, due to the limitations of spatial resolution and contrast, this has been difficult to achieve in awake subjects. Here, we report that by using a combination of MR microscopy and novel contrast effects, cortical layers can be delineated in the visual cortex of awake subjects (nonhuman primates) at 4.7 T. We obtained data from 30-min acquisitions at voxel size of 62.5 × 62.5 × 1000 μm(3) (4 nl). Both the phase and magnitude components of the T(2)*-weighted image were used to generate laminar profiles which are believed to reflect variations in myelin and local cell density content across cortical depth. Based on this, we were able to identify six layers characteristic of the striate cortex (V1). These were the stripe of Kaes-Bechterew (in layer II/III), the stripe of Gennari (in layer IV), the inner band of Baillarger (in layer V), as well as three sub-layers within layer IV (IVa, IVb, and IVc). Furthermore, we found that the laminar structure of two extrastriate visual cortex (V2, V4) can also be detected. Following the tradition of Brodmann, this significant improvement in cortical laminar visualization should make it possible to discriminate cortical regions in awake subjects corresponding to differences in myeloarchitecture and cytoarchitecture.
Copyright © 2011 Elsevier Inc. All rights reserved.
PURPOSE - The purpose of this study was to validate a two-regression model for predicting energy expenditure (EE) from ActiGraph GT1M accelerometer-generated activity counts using a whole-room indirect calorimeter and the doubly labeled water (DLW) technique. We also investigated if a low-pass filter (LPF) approach would improve the model's accuracy in the minute-to-minute EE prediction.
METHODS - Thirty-four healthy volunteers (age = 20-67 yr, body mass index = 19.3-52.1 kg.m) spent approximately 24 h in a room calorimeter while wearing a GT1M monitor and performed structured and self-selected activities followed by overnight sleep. The EE predicted by the models and expressed in metabolic equivalents (MET-minutes) during waking times was compared with the room calorimeter-measured EE. A subset of volunteers (n = 22) completed a 14-d DLW protocol in free living while wearing an ActiGraph. The average daily EE predicted by the models (MET-minutes) was compared with the DLW.
RESULTS - Compared with the room calorimeter, the two-regression model overpredicted EE by 10.2% +/- 11.4% (1282 +/- 125 and 1174 +/- 152 MET.min, P < 0.001) and time spent in moderate physical activity (PA) by 36.9 +/- 46.0 min while underestimating the time spent in light PA by -48.3 +/- 55.0 min (P < 0.05). The LPF reduced the squared and mean absolute error in the EE prediction (P < 0.05) but not the prediction error in time spent in moderate or light PA (both P > 0.05). The EE measured by DLW (2108 +/- 358 MET.min.d) and predicted by both filtered and unfiltered models (2104 +/- 218 and 2192 +/- 228 MET.min.d, respectively) were similar (P > 0.05).
CONCLUSIONS - The two-regression model with LPF showed good agreement with total EE measured using room calorimeter and DLW. However, the individual variability in assessing time spent in sedentary, low, and moderate PA intensities and related EE remains significant.
Movement sensing using accelerometers is commonly used for the measurement of physical activity (PA) and estimating energy expenditure (EE) under free-living conditions. The major limitation of this approach is lack of accuracy and precision in estimating EE, especially in low-intensity activities. Thus the objective of this study was to investigate benefits of a distributed lag spline (DLS) modeling approach for the prediction of total daily EE (TEE) and EE in sedentary (1.0-1.5 metabolic equivalents; MET), light (1.5-3.0 MET), and moderate/vigorous (> or = 3.0 MET) intensity activities in 10- to 17-year-old youth (n = 76). We also explored feasibility of the DLS modeling approach to predict physical activity EE (PAEE) and METs. Movement was measured by Actigraph accelerometers placed on the hip, wrist, and ankle. With whole-room indirect calorimeter as the reference standard, prediction models (Hip, Wrist, Ankle, Hip+Wrist, Hip+Wrist+Ankle) for TEE, PAEE, and MET were developed and validated using the fivefold cross-validation method. The TEE predictions by these DLS models were not significantly different from the room calorimeter measurements (all P > 0.05). The Hip+Wrist+Ankle predicted TEE better than other models and reduced prediction errors in moderate/vigorous PA for TEE, MET, and PAEE (all P < 0.001). The Hip+Wrist reduced prediction errors for the PAEE and MET at sedentary PA (P = 0.020 and 0.021) compared with the Hip. Models that included Wrist correctly classified time spent at light PA better than other models. The means and standard deviations of the prediction errors for the Hip+Wrist+Ankle and Hip were 0.4 +/- 144.0 and 1.5 +/- 164.7 kcal for the TEE, 0.0 +/- 84.2 and 1.3 +/- 104.7 kcal for the PAEE, and -1.1 +/- 97.6 and -0.1 +/- 108.6 MET min for the MET models. We conclude that the DLS approach for accelerometer data improves detailed EE prediction in youth.
Normal human consciousness may be impaired by two possible routes: direct reduced function in widespread cortical regions or indirect disruption of subcortical activating systems. The route through which temporal lobe limbic seizures impair consciousness is not known. We recently developed an animal model that, like human limbic seizures, exhibits neocortical deactivation including cortical slow waves and reduced cortical cerebral blood flow (CBF). We now find through functional magnetic resonance imaging (fMRI) that electrically stimulated hippocampal seizures in rats cause increased activity in subcortical structures including the septal area and mediodorsal thalamus, along with reduced activity in frontal, cingulate, and retrosplenial cortex. Direct recordings from the hippocampus, septum, and medial thalamus demonstrated fast poly-spike activity associated with increased neuronal firing and CBF, whereas frontal cortex showed slow oscillations with decreased neuronal firing and CBF. Stimulation of septal area, but not hippocampus or medial thalamus, in the absence of a seizure resulted in cortical deactivation with slow oscillations and behavioral arrest, resembling changes seen during limbic seizures. Transecting the fornix, the major route from hippocampus to subcortical structures, abolished the negative cortical and behavioral effects of seizures. Cortical slow oscillations and behavioral arrest could be reconstituted in fornix-lesioned animals by inducing synchronous activity in the hippocampus and septal area, implying involvement of a downstream region converged on by both structures. These findings suggest that limbic seizures may cause neocortical deactivation indirectly, through impaired subcortical function. If confirmed, subcortical networks may represent a target for therapies aimed at preserving consciousness in human temporal lobe seizures.
OBJECTIVE - Insulin represses the expression of gluconeogenic genes at the mRNA level, but the hormone appears to have only weak inhibitory effects in vivo. The aims of this study were 1) to determine the maximal physiologic effect of insulin, 2) to determine the relative importance of its effects on gluconeogenic regulatory sites, and 3) to correlate those changes with alterations at the cellular level.
RESEARCH DESIGN AND METHODS - Conscious 60-h fasted canines were studied at three insulin levels (near basal, 4x, or 16x) during a 5-h euglycemic clamp. Pancreatic hormones were controlled using somatostatin with portal insulin and glucagon infusions. Glucose metabolism was assessed using the arteriovenous difference technique, and molecular signals were assessed.
RESULTS - Insulin reduced gluconeogenic flux to glucose-6-phosphate (G6P) but only at the near-maximal physiological level (16x basal). The effect was modest compared with its inhibitory effect on net hepatic glycogenolysis, occurred within 30 min, and was associated with a marked decrease in hepatic fat oxidation, increased liver fructose 2,6-bisphosphate level, and reductions in lactate, glycerol, and amino acid extraction. No further diminution in gluconeogenic flux to G6P occurred over the remaining 4.5 h of the study, despite a marked decrease in PEPCK content, suggesting poor control strength for this enzyme in gluconeogenic regulation in canines.
CONCLUSIONS - Gluconeogenic flux can be rapidly inhibited by high insulin levels in canines. Initially decreased hepatic lactate extraction is important, and later reduced gluconeogenic precursor availability plays a role. Changes in PEPCK appear to have little or no acute effect on gluconeogenic flux.