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Exploration of human consciousness remains a final frontier within basic neuroscience; that is, how the finite biological structure and function of the brain give rise to the seemingly infinite expanse that encompasses the terrain of the mind. Contemporary mindfulness and other contemplative practices across historical and post-modern traditions involve systematic forms of mental training that allow a practitioner to develop the mind in very specific and quantifiable ways. While there has been some progress identifying specific electrophysiological markers of meditation, some fundamental questions remain to this scientific enquiry; (1) how to concisely classify discrete and developmentally specific 'mind states' of consciousness that are in line with the subtle complex phenomenology of experience so to yield ontological quantifications? (2) what measures best represent such classification/quantification systems? (3) can the present electrophysiological purview map developmentally specified mind states and stages to neurobiological substrates, based on extant contention (i.e. discrete EEG band functionality, phenomenological significance, and underlying mechanisms) regarding the interpretation of EEG physiology/morphology?
Copyright © 2019 Elsevier Ltd. All rights reserved.
Traumatic brain injury (TBI) is a looming epidemic, growing most rapidly in the elderly population. Some of the most devastating sequelae of TBI are related to depressed levels of consciousness (e.g., coma, minimally conscious state) or deficits in executive function. To date, pharmacological and rehabilitative therapies to treat these sequelae are limited. Deep brain stimulation (DBS) has been used to treat a number of pathologies, including Parkinson disease, essential tremor, and epilepsy. Animal and clinical research shows that targets addressing depressed levels of consciousness include components of the ascending reticular activating system and areas of the thalamus. Targets for improving executive function are more varied and include areas that modulate attention and memory, such as the frontal and prefrontal cortex, fornix, nucleus accumbens, internal capsule, thalamus, and some brainstem nuclei. The authors review the literature addressing the use of DBS to treat higher-order cognitive dysfunction and disorders of consciousness in TBI patients, while also offering suggestions on directions for future research.
Neurobiological theories of awareness propose divergent accounts of the spatial extent of brain changes that support conscious perception. Whereas focal theories posit mostly local regional changes, global theories propose that awareness emerges from the propagation of neural signals across a broad extent of sensory and association cortex. Here we tested the scalar extent of brain changes associated with awareness using graph theoretical analysis applied to functional connectivity data acquired at ultra-high field while subjects performed a simple masked target detection task. We found that awareness of a visual target is associated with a degradation of the modularity of the brain's functional networks brought about by an increase in intermodular functional connectivity. These results provide compelling evidence that awareness is associated with truly global changes in the brain's functional connectivity.
Even during moments when we fail to be fully aware of our environment, our brains never go silent. Instead, it appears that the brain can also operate in an alternate, unconscious mode. Delineating unconscious from conscious neural processes is a promising first step toward investigating how awareness emerges from brain activity. Here we focus on recent insights into the neuronal processes that contribute to visual function in the absence of a conscious visual percept. Drawing on insights from findings on the phenomenon of blindsight that results from injury to primary visual cortex and the results of experimentally induced perceptual suppression, we describe what kind of visual information the visual system analyzes unconsciously and we discuss the neuronal routing and responses that accompany this process. We conclude that unconscious processing of certain visual stimulus attributes, such as the presence of visual motion or the emotional expression of a face can occur in a geniculo-cortical circuit that runs independent from and in parallel to the predominant route through primary visual cortex. We speculate that in contrast, bidirectional neuronal interactions between cortex and the thalamic pulvinar nucleus that support large-scale neuronal integration and visual awareness are impeded during blindsight and perceptual suppression.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Obesity and type 2 diabetes lessen the quality of life of those afflicted and place considerable burden on the healthcare system. Furthermore, the detrimental impact of these pathologies is expected to persist or even worsen. Diabetes is characterized by impaired insulin action and glucose homeostasis. This has led to a rapid increase in the number of mouse models of metabolic disease being used in the basic sciences to assist in facilitating a greater understanding of the metabolic dysregulation associated with obesity and diabetes, the identification of therapeutic targets, and the discovery of effective treatments. This review briefly describes the most frequently utilized models of metabolic disease. A presentation of standard methods and technologies on the horizon for assessing metabolic phenotypes in mice, with particular emphasis on glucose handling and energy balance, is provided. The article also addresses issues related to study design, selection and execution of metabolic tests of glucose metabolism, the presentation of data, and interpretation of results.
This essay critically examines the extent to which binocular rivalry can provide important clues about the neural correlates of conscious visual perception. Our ideas are presented within the framework of four questions about the use of rivalry for this purpose: (i) what constitutes an adequate comparison condition for gauging rivalry's impact on awareness, (ii) how can one distinguish abolished awareness from inattention, (iii) when one obtains unequivocal evidence for a causal link between a fluctuating measure of neural activity and fluctuating perceptual states during rivalry, will it generalize to other stimulus conditions and perceptual phenomena and (iv) does such evidence necessarily indicate that this neural activity constitutes a neural correlate of consciousness? While arriving at sceptical answers to these four questions, the essay nonetheless offers some ideas about how a more nuanced utilization of binocular rivalry may still provide fundamental insights about neural dynamics, and glimpses of at least some of the ingredients comprising neural correlates of consciousness, including those involved in perceptual decision-making.
OBJECTIVES - To test the hypothesis that low bispectral index scores and low sedative requirements during therapeutic hypothermia predict poor neurologic outcome.
DESIGN - Observational study of a prospectively collected cohort.
SETTING - Cardiovascular ICU.
PATIENTS - One hundred sixty consecutive cardiac arrest patients treated with therapeutic hypothermia.
INTERVENTIONS - None.
MEASUREMENTS AND RESULTS - Eighty-four of the 141 subjects (60%) who survived hypothermia induction were discharged from the ICU with poor neurologic outcome, defined as a cerebral performance category score of 3, 4, or 5. These subjects had lower bispectral index (p < 0.001) and sedative requirements (p < 0.001) during hypothermia compared with the 57 subjects discharged with good outcome. Early prediction of neurologic recovery was best 7 hours after ICU admission, and median bispectral index scores at that time were 31 points lower in subjects discharged with poor outcome (11 [interquartile range, 4-29] vs 42 [37-49], p < 0.001). Median sedation requirements decreased by 17% (interquartile range, -50 to 0%) 7 hours after ICU admission in subjects with poor outcome but increased by 50% (interquartile range, 0-142%) in subjects with good outcome (p < 0.001). Each 10-point decrease in bispectral index was independently associated with a 59% increase in the odds of poor outcome (95% CI, 32-76%; p < 0.001). The model including bispectral index and sedative requirement correctly reclassified 15% of subjects from good to poor outcome and 1% of subjects from poor to good outcome. The model incorrectly reclassified 1% of subjects from poor to good outcome but did not incorrectly reclassify any from good to poor outcome.
CONCLUSIONS - Bispectral index scores and sedative requirements early in the course of therapeutic hypothermia improve the identification of patients who will not recover from brain anoxia. The ability to accurately predict nonrecovery after cardiac arrest could facilitate discussions with families, reduce patient suffering, and limit use of ICU resources in futile cases.
The impact of the GLP-1 receptor agonist lixisenatide on postprandial glucose disposition was examined in conscious dogs to identify mechanisms for its improvement of meal tolerance in humans and examine the tissue disposition of meal-derived carbohydrate. Catheterization for measurement of hepatic balance occurred ≈16 days before study. After being fasted overnight, dogs received a subcutaneous injection of 1.5 μg/kg lixisenatide or vehicle (saline, control; n = 6/group). Thirty minutes later, they received an oral meal feeding (93.4 kJ; 19% protein, 71% glucose polymers, and 10% lipid). Acetaminophen was included in the meal in four control and five lixisenatide dogs for assessment of gastric emptying. Observations continued for 510 min; absorption was incomplete in lixisenatide at that point. The plasma acetaminophen area under the curve (AUC) in lixisenatide was 65% of that in control (P < 0.05). Absorption of the meal began within 15 min in control but was delayed until ≈30-45 min in lixisenatide. Lixisenatide reduced (P < 0.05) the postprandial arterial glucose AUC ≈54% and insulin AUC ≈44%. Net hepatic glucose uptake did not differ significantly between groups. Nonhepatic glucose uptake tended to be reduced by lixisenatide (6,151 ± 4,321 and 10,541 ± 1,854 μmol·kg(-1)·510 min(-1) in lixisenatide and control, respectively; P = 0.09), but adjusted (for glucose and insulin concentrations) values did not differ (18.9 ± 3.8 and 19.6 ± 7.9 l·kg(-1)·pmol(-1)·l(-1), lixisenatide and control, respectively; P = 0.94). Thus, lixisenatide delays gastric emptying, allowing more efficient disposal of the carbohydrate in the feeding without increasing liver glucose disposal. Lixisenatide could prove to be a valuable adjunct in treatment of postprandial hyperglycemia in impaired glucose tolerance or type 2 diabetes.
BACKGROUND - Temporal lobectomy can lead to favorable seizure outcomes in medically-refractory temporal lobe epilepsy (TLE). Although most studies focus on seizure freedom after temporal lobectomy, less is known about seizure semiology in patients who "fail" surgery. Morbidity differs between seizure types that impair or spare consciousness. Among TLE patients with seizures after surgery, how does temporal lobectomy influence seizure type and frequency?
OBJECTIVE - To characterize seizure types and frequencies before and after temporal lobectomy for TLE, including consciousness-sparing or consciousness-impairing seizures.
METHODS - We performed a retrospective longitudinal cohort study examining patients undergoing temporal lobectomy for epilepsy at our institution from January 1995 to August 2010.
RESULTS - Among 241 TLE patients who received temporal lobectomy, 174 (72.2%) patients achieved Engel class I outcome (free of disabling seizures), including 141 (58.5%) with complete seizure freedom. Overall seizure frequency in patients with persistent postoperative seizures decreased by 70% (P < .01), with larger reductions in consciousness-impairing seizures. While the number of patients experiencing consciousness-sparing simple partial seizures decreased by only 19% after surgery, the number of individuals having consciousness-impairing complex partial seizures and generalized tonic-clonic seizures diminished by 70% and 68%, respectively (P < .001). Simple partial seizure was the predominant seizure type in 19.1% vs 37.0% of patients preoperatively and postoperatively, respectively (P < .001). Favorable seizure outcome was predicted by a lack of generalized seizures preoperatively (odds ratio 1.74, 95% confidence interval 1.06-2.86, P < .5).
CONCLUSION - Given important clinical and mechanistic differences between seizures with or without impairment of consciousness, seizure type and frequency remain important considerations in epilepsy surgery.
PURPOSE - Most children with medically refractory temporal lobe epilepsy (TLE) become seizure free after temporal lobectomy, but some individuals continue to seize. As studies of temporal lobectomy typically focus on seizure freedom, the effect of surgery on seizure type and frequency among children with persistent seizures is poorly understood. Seizures which impair consciousness are associated with increased morbidity compared to consciousness-sparing seizures.
METHODS - A retrospective cohort study was performed to evaluate the effects of temporal lobectomy on seizure type and frequency in children with intractable TLE.
RESULTS - Among 58 pediatric TLE patients with a mean (±SEM) age of 14.0 ± 0.7 years who received temporal lobectomy, 46 (79.3%) individuals achieved an Engel class I seizure outcome, including 38 (65.5%) children who became completely seizure free (Engel IA). Mean follow-up was 2.7 ± 0.4 years. While the number of patients experiencing simple partial seizures (SPSs) (consciousness sparing) decreased by only 23 % after surgery, the number of children having complex partial seizures and generalized tonic-clonic seizures (consciousness impairing) diminished by 87 and 83%, respectively (p < 0.01). SPS was the predominant seizure type in only 11.3% of patients before resection, but in 42.1% of patients with postoperative seizures (p < 0.01). Children with postoperative seizures experienced a 70% reduction in overall seizure frequency compared to baseline (p < 0.05), having consciousness-impairing seizures 94% less frequently (p < 0.05), but having consciousness-sparing seizures 35% more frequently (p = 0.73).
CONCLUSIONS - Seizure type and frequency are important considerations in the medical and surgical treatment of children with epilepsy, although complete seizure freedom remains the ultimate goal.