Fly-by-light flight control system technology development plan

The results of a four-month, phased effort to develop a Fly-by-Light Technology Development Plan are documented. The technical shortfalls for each phase were identified and a development plan to bridge the technical gap was developed. The production configuration was defined for a 757-type airplane, but it is suggested that the demonstration flight be conducted on the NASA Transport Systems Research Vehicle. The modifications required and verification and validation issues are delineated in this report. A detailed schedule for the phased introduction of fly-by-light system components has been generated. It is concluded that a fiber-optics program would contribute significantly toward developing the required state of readiness that will make a fly-by-light control system not only cost effective but reliable without mitigating the weight and high-energy radio frequency related benefits

Coupling between gamma-band power and cerebral blood volume during recurrent acute neocortical seizures

Characterization of neural and hemodynamic biomarkers of epileptic activity that can be measured using non-invasive techniques is fundamental to the accurate identification of the epileptogenic zone (EZ) in the clinical setting. Recently, oscillations at gamma-band frequencies and above (>30 Hz) have been suggested to provide valuable localizing information of the EZ and track cortical activation associated with epileptogenic processes. Although a tight coupling between gamma-band activity and hemodynamic-based signals has been consistently demonstrated in non-pathological conditions, very little is known about whether such a relationship is maintained in epilepsy and the laminar etiology of these signals. Confirmation of this relationship may elucidate the underpinnings of perfusion-based signals in epilepsy and the potential value of localizing the EZ using hemodynamic correlates of pathological rhythms. Here, we use concurrent multi-depth electrophysiology and 2-dimensional optical imaging spectroscopy to examine the coupling between multi-band neural activity and cerebral blood volume (CBV) during recurrent acute focal neocortical seizures in the urethane-anesthetized rat. We show a powerful correlation between gamma-band power (25-90 Hz) and CBV across cortical laminae, in particular layer 5, and a close association between gamma measures and multi-unit activity (MUA). Our findings provide insights into the laminar electrophysiological basis of perfusion-based imaging signals in the epileptic state and may have implications for further research using non-invasive multi-modal techniques to localize epileptogenic tissue

A Bird’s Eye View of Human Language Evolution

Comparative studies of linguistic faculties in animals pose an evolutionary paradox: language involves certain perceptual and motor abilities, but it is not clear that this serves as more than an input–output channel for the externalization of language proper. Strikingly, the capability for auditory–vocal learning is not shared with our closest relatives, the apes, but is present in such remotely related groups as songbirds and marine mammals. There is increasing evidence for behavioral, neural, and genetic similarities between speech acquisition and birdsong learning. At the same time, researchers have applied formal linguistic analysis to the vocalizations of both primates and songbirds. What have all these studies taught us about the evolution of language? Is the comparative study of an apparently species-specific trait like language feasible? We argue that comparative analysis remains an important method for the evolutionary reconstruction and causal analysis of the mechanisms underlying language. On the one hand, common descent has been important in the evolution of the brain, such that avian and mammalian brains may be largely homologous, particularly in the case of brain regions involved in auditory perception, vocalization, and auditory memory. On the other hand, there has been convergent evolution of the capacity for auditory–vocal learning, and possibly for structuring of external vocalizations, such that apes lack the abilities that are shared between songbirds and humans. However, significant limitations to this comparative analysis remain. While all birdsong may be classified in terms of a particularly simple kind of concatenation system, the regular languages, there is no compelling evidence to date that birdsong matches the characteristic syntactic complexity of human language, arising from the composition of smaller forms like words and phrases into larger ones

Comparison of stimulus-evoked cerebral hemodynamics in the awake mouse and under a novel anesthetic regime

Neural activity is closely followed by a localised change in cerebral blood flow, a process termed neurovascular coupling. These hemodynamic changes form the basis of contrast in functional magnetic resonance imaging (fMRI) and are used as a correlate for neural activity. Anesthesia is widely employed in animal fMRI and neurovascular studies, however anesthetics are known to profoundly affect neural and vascular physiology, particularly in mice. Therefore, we investigated the efficacy of a novel ‘modular’ anesthesia that combined injectable (fentanyl-fluanisone/midazolam) and volatile (isoflurane) anesthetics in mice. To characterize sensory-evoked cortical hemodynamic responses, we used optical imaging spectroscopy to produce functional maps of changes in tissue oxygenation and blood volume in response to mechanical whisker stimulation. Following fine-tuning of the anesthetic regime, stimulation elicited large and robust hemodynamic responses in the somatosensory cortex, characterized by fast arterial activation, increases in total and oxygenated hemoglobin, and decreases in deoxygenated hemoglobin. Overall, the magnitude and speed of evoked hemodynamic responses under anesthesia resembled those in the awake state, indicating that the novel anesthetic combination significantly minimizes the impact of anesthesia. Our findings have broad implications for both neurovascular research and longitudinal fMRI studies that increasingly require the use of genetically engineered mice

Enhanced cerebral blood volume under normobaric hyperoxia in the J20-hAPP mouse model of Alzheimer’s disease

Early impairments to neurovascular coupling have been proposed to be a key pathogenic factor in the onset and progression of Alzheimer’s disease (AD). Studies have shown impaired neurovascular function in several mouse models of AD, including the J20-hAPP mouse. In this study, we aimed to investigate early neurovascular changes using wild-type (WT) controls and J20-hAPP mice at 6 months of age, by measuring cerebral haemodynamics and neural activity to physiological sensory stimulations. A thinned cranial window was prepared to allow access to cortical vasculature and imaged using 2D-optical imaging spectroscopy (2D-OIS). After chronic imaging sessions where the skull was intact, a terminal acute imaging session was performed where an electrode was inserted into the brain to record simultaneous neural activity. We found that cerebral haemodynamic changes were significantly enhanced in J20-hAPP mice compared with controls in response to physiological stimulations, potentially due to the significantly higher neural activity (hyperexcitability) seen in the J20-hAPP mice. Thus, neurovascular coupling remained preserved under a chronic imaging preparation. Further, under hyperoxia, the baseline blood volume and saturation of all vascular compartments in the brains of J20-hAPP mice were substantially enhanced compared to WT controls, but this effect disappeared under normoxic conditions. This study highlights novel findings not previously seen in the J20-hAPP mouse model, and may point towards a potential therapeutic strategy

Key aspects of neurovascular control mediated by specific populations of inhibitory cortical interneurons

Inhibitory interneurons can evoke vasodilation and vasoconstriction, making them potential cellular drivers of neurovascular coupling. However, the specific regulatory roles played by particular interneuron subpopulations remain unclear. Our purpose was therefore to adopt a cell-specific optogenetic approach to investigate how somatostatin (SST) and neuronal nitric oxide synthase (nNOS)-expressing interneurons might influence the neurovascular relationship. In mice, specific activation of SST- or nNOS-interneurons was sufficient to evoke haemodynamic changes. In the case of nNOS-interneurons, robust haemodynamic changes occurred with minimal changes in neural activity, suggesting that the ability of BOLD fMRI to reliably reflect changes in neuronal activity may be dependent on type of neuron recruited. Conversely, activation of SST-interneurons produced robust changes in evoked neural activity with shallow cortical excitation and pronounced deep layer cortical inhibition. Prolonged activation of SST-interneurons often resulted in an increase in blood volume in the centrally activated area with an accompanying blood volume decrease in surrounding brain regions, analogous to the negative BOLD signal. These results demonstrate the role of specific populations of cortical interneurons in the active control of neurovascular function

Melanoma: What are the gaps in our knowledge?

Jonathan Rees outlines a number of puzzling gaps that remain in our knowledge of the etiology of non-acral melanomas

Contralateral dissociation between neural activity and cerebral blood volume during recurrent acute focal neocortical seizures

OBJECTIVE: Whether epileptic events disrupt normal neurovascular coupling mechanisms locally or remotely is unclear. We sought to investigate neurovascular coupling in an acute model of focal neocortical epilepsy, both within the seizure onset zone and in contralateral homotopic cortex. METHODS: Neurovascular coupling in both ipsilateral and contralateral vibrissal cortices of the urethane-anesthetized rat were examined during recurrent 4-aminopyridine (4-AP, 15 mm, 1 μl) induced focal seizures. Local field potential (LFP) and multiunit spiking activity (MUA) were recorded via two bilaterally implanted 16-channel microelectrodes. Concurrent two-dimensional optical imaging spectroscopy was used to produce spatiotemporal maps of cerebral blood volume (CBV). RESULTS: Recurrent acute seizures in right vibrissal cortex (RVC) produced robust ipsilateral increases in LFP and MUA activity, most prominently in layer 5, that were nonlinearly correlated to local increases in CBV. In contrast, contralateral left vibrissal cortex (LVC) exhibited relatively smaller nonlaminar specific increases in neural activity coupled with a decrease in CBV, suggestive of dissociation between neural and hemodynamic responses. SIGNIFICANCE: These findings provide insights into the impact of epileptic events on the neurovascular unit, and have important implications both for the interpretation of perfusion-based imaging signals in the disorder and understanding the widespread effects of epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here

Drawbacks of a Dual Systems Approach to Family Firms: Can We Expand Our Thinking?

Conceptualizing the family firm as a dual system with properties of both the family and the business has prevented the field from fully examining the nature of these firms and has biased our observations and interventions. Too narrow a focus on the contribution of subsystems leads to a stereotyping of subsystem functioning, inconsistent and inadequate analysis of interpersonal dynamics, exaggerated notions of subsystem boundaries, and an underanalysis of whole system characteristics. Each of these drawbacks is discussed, and a beginning view of the family firm as a single entity is presented.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67216/2/10_1111_j_1741-6248_1991_00383_x.pd