A microscopically motivated theory of glassy dynamics based on an underlying random first order transition is developed to explain the magnitude of free energy barriers for glassy relaxation. A variety of empirical correlations embodied in the concept of liquid "fragility" are shown to be quantitatively explained by such a model. The near universality of a Lindemann ratio characterizing the maximal amplitude of thermal vibrations within an amorphous minimum explains the variation of fragility with a liquid's configurational heat capacity density. Furthermore, the numerical prefactor of this correlation is well approximated by the microscopic calculation. The size of heterogeneous reconfiguring regions in a viscous liquid is inferred and the correlation of nonexponentiality of relaxation with fragility is qualitatively explained. Thus the wide variety of kinetic behavior in liquids of quite disparate chemical nature reflects quantitative rather than qualitative differences in their energy landscapes.I t is believed that all classical fluids could form glasses if cooled sufficiently fast so as to avoid crystallization. Central to glass formation is a dramatic slowing of molecular motions on cooling the liquid. The existence of a universal description of glass transitions is suggested by empirical observations connecting deviations from the Arrhenius law for the slowing of rates, nonexponential relaxations in the super cooled liquid state, and the behavior of thermodynamic properties on cooling (1). Quantitative differences in behavior of different substances sometimes obscure this universality. This has led to a classification of liquids into "fragile" ones like o-terphenyl, having the most dramatic deviations from the Arrhenius law, and into "strong" ones like pure SiO 2 where the Arrhenius equation works well (1). In this paper, we show how the fragile versus strong behavior of liquids can be understood within a microscopically motivated theory based on the idea that glassy dynamics is caused by an underlying thermodynamic, ideal "random first order" transition (2-7).The notion that a random first order transition lies at the heart of glass formation received its early theoretical support from the remarkable confluence of approximate microscopic theories of the liquid glass transition (8-10) and the behavior of a large class of exactly solvable statistical mechanical models of spin glasses with quenched disorder (11). Two closely connected theories of the liquid glass transition suggest features similar to first order transitions. One of these, the so-called mode-mode coupling theory (8, 12), focuses on the feedback between the slow fluctuations of fluid density in a molecule's environment on the motion of that molecule. This theory predicts a sharp transition in the dynamics as well as a characteristic behavior of the time correlation functions near the predicted transition. Mössbauer effect (13) and neutron scattering (14) are roughly consistent with these precursor phenomena. At temperatures below the transit...

Recent experiments and computer simulations show that supercooled liquids around the glass transition temperature are "dynamically heterogeneous" [1]. Such heterogeneity is expected from the random first order transition theory of the glass transition. Using a microscopic approach based on this theory, we derive a relation between the departure from Debye relaxation as characterized by the β value of a stretched exponential response function φ(t) = e −(t/τ KW W )β , and the fragility of the liquid. The β value is also predicted to depend on temperature and to vanish as the ideal glass transition is approached at the Kauzmann temperature. 64.70.PfThe striking universality of relaxation dynamics in supercooled liquids has remained intriguing for decades. In addition to the overall dramatic slowing of transport as the glass transition is approached, one finds the emergence of a strongly non-exponential approach to equilibrium when a supercooled liquid is perturbed. This contrasts with the behavior of chemically simple liquids at higher temperatures, where only a single time scale for a highly exponential structural relaxation is usually encountered for times beyond the vibrational time scales. Both the range of time scales and the median magnitude of the relaxation time require explanation.Several theoretical threads lead to the notion that the universal behavior of supercooled liquids arises from proximity to an underlying random first order transition [2-6] which is found in mean field theories of spin glass without reflection symmetry [7][8][9], and in mode coupling [10,11] and density functional [12][13][14] approaches to the structural glass transition. This picture explains both the breakdown of simple collisional theories of transport that apply to high temperature liquids at a characteristic temperature T A and the impending entropy crisis of supercooled liquids first discovered by Simon and brilliantly emphasized by Kauzmann [15] at the temperature T K . Furthermore the scenario suggests that the finite range of the underlying force modifies mean field behavior between T A and T K in a way that leads to an intricate "mosaic" structure of a glassy fluid in which mesoscopic local regions are individually each in an aperiodic minimum but are separated by more mobile domain walls which are strained and quite far from local minima structures [16]. Relaxation of the elements of the mosaic, reconfiguring to other low energy structures, leads to the slow relaxation and a scaling treatment of the median relaxation The spatial heterogeneity implied by the mosaic picture has received strong support from recent computer simulations [19,20] and laboratory experiments, especially direct measurements using 4-D NMR [21] and optical hole burning [22] techniques. In the mosaic picture, different regions of the supercooled liquid will relax in different ways depending on how stable the local structure is, but for time scales much longer than the median, the system will behave homogeneously since the neighboring elements of ...

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The pathological and radiological hallmarks of multiple sclerosis (MS) include multiple demyelinated lesions disseminated throughout the white matter of the central nervous system (CNS). More recently, the cerebral cortex has been shown to be affected in MS, but the elucidation of events causing cortical demyelination has been hampered by the lack of animal models reflecting such human cortical pathology. In this report, we have described the presence of cortical gray matter and callosal white matter demyelinating lesions in the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Similar to the pathological lesions of MS patients, EAE lesions have been classified as type I-leukocortical, type II-intracortical and type III-subpial. All of these lesions had varying degrees of demyelination, inflammatory cells and reactive astrocytes. Similar to MS, cortical layers during EAE showed demyelination, microglia activation, synaptic protein alterations and apoptotic cells. In addition, the callosal white matter during EAE had many inflammatory demyelinating lesions and axon degeneration. Functional electrophysiological conduction analysis showed deficits in both myelinated and unmyelinated callosal axons during early and late EAE. The chronic EAE mouse model has features that mimic cortical and callosal pathology of MS, and can be potentially used to screen agents to prevent these features of disease.

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Transcranial direct current stimulation (tDCS)1 has been reported to be a promising technique for consciousness improvement for patients with disorders of consciousness (DOC).2 However, there has been no direct electrophysiological evidence to demonstrate the efficacy of tDCS on patients with DOC. Therefore, we aim to measure the cortical excitability changes induced by tDCS in patients with DOC, to find electrophysiological evidence supporting the therapeutic efficacy of tDCS on patients with DOC. In this study, we enrolled sixteen patients with DOC, including nine vegetative state (VS)3 and seven minimally conscious state (MCS)4 (six females and ten males). TMS-EEG was applied to assess cortical excitability changes after twenty minutes of anodal tDCS of the left dorsolateral prefrontal cortex. Global cerebral excitability were calculated to quantify cortical excitability in the temporal domain: four time intervals (0–100, 100–200, 200–300, 300-400 ms). Then local cerebral excitability in the significantly altered time windows were investigated (frontal, left/right hemispheres, central, and posterior). Compared to baseline and sham stimulation, we found that global cerebral excitability increased in early time windows (0–100 and 100-200 ms) for patients with MCS; for the patients with VS, global cerebral excitability increased in the 0-100 ms interval but decreased in the 300-400 ms interval. The local cerebral excitability was significantly different between MCS and VS. The results indicated that tDCS can effectively modulate the cortical excitability of patients with DOC; and the changes in excitability in temporal and spatial domains are different between patients with MCS and those with VS.

BackgroundWhile repetitive transcranial magnetic stimulation (rTMS) has been applied in treatment of patients with disorders of consciousness (DOC), a standardized stimulation protocol has not been proposed, and its therapeutic effects are inconsistently documented.ObjectivesTo assess the efficacy of rTMS in improving consciousness in patients with persistent minimally conscious state (MCS) or unresponsive wakefulness syndrome (UWS), previously known as vegetative state (VS).MethodA prospective single-blinded study, with selected subjects, was carried out. In total, 16 patients (5 MCS and 11 VS/UWS) with chronic DOC were included. All patients received active 10 Hz rTMS at the left dorsolateral prefrontal cortex (DLPFC), at one session per day, for 20 consecutive days. A single daily session of stimulation consisted of 1,000 pulses (10 s of 10 Hz trains; repeated 10 times with an inter-train interval of 60 s; and 11 min and 40 s for total session). The main outcome measures were changes in the total score on the JFK Coma Recovery Scale-Revised (CRS-R) scale. Additional measures were the impressions of caregivers after the conclusion of the interventions, which were assessed using the Clinical Global Impression-Improvement (CGI-I) scale.ResultsThe CRS-R scores were increased in all 5 MCS patients and 4 of 11 VS/UWS patients, while a significant enhancement of CRS-R scores was observed compared to the baseline in all participants (p = 0.007). However, the improvement was more notable in MCS patients (p = 0.042) than their VS/UWS counterparts (p = 0.066). Based on the CGI-I scores, two patients improved considerably, two improved, six minimally improved, six experienced no change, and none deteriorated. Good concordance was seen between the CGI-I result and the increases in CRS-R scores.ConclusionTreatment of 10 Hz multisession rTMS applied to the left DLPFC is promising for the rehabilitation of DOC patients, especially those in MCS. Further validation with a cohort of a larger sample size is required.

Recently, neuroimaging technologies have been developed as important methods for assessing the brain condition of patients with disorders of consciousness (DOC). Among these technologies, resting-state electroencephalography (EEG) recording and analysis has been widely applied by clinicians due to its relatively low cost and convenience. EEG reflects the electrical activity of the underlying neurons, and it contains information regarding neuronal population oscillations, the information flow pathway, and neural activity networks. Some features derived from EEG signal processing methods have been proposed to describe the electrical features of the brain with DOC. The computation of these features is challenging for clinicians working to comprehend the corresponding physiological meanings and then to put them into clinical applications. This paper reviews studies that analyze spontaneous EEG of DOC, with the purpose of diagnosis, prognosis, and evaluation of brain interventions. It is expected that this review will promote our understanding of the EEG characteristics in DOC.