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Emerging research on neuroplasticity processes in psychosis spectrum illnesses—from the synaptic to the macrocircuit levels—fill key gaps in our models of pathophysiology and open up important treatment considerations. In this selective narrative review, we focus on three themes, emphasizing alterations in spike-timing dependent and Hebbian plasticity that occur during adolescence, the critical period for prefrontal system development: (1) Experience-dependent dysplasticity in psychosis emerges from activity decorrelation within neuronal ensembles. (2) Plasticity processes operate bidirectionally: deleterious environmental and experiential inputs shape microcircuits. (3) Dysregulated plasticity processes interact across levels of scale and time and include compensatory mechanisms that have pathogenic importance. We present evidence that—given the centrality of progressive dysplastic changes, especially in prefrontal cortex—pharmacologic or neuromodulatory interventions will need to be supplemented by corrective learning experiences for the brain if we are to help people living with these illnesses to fully thrive.

Anhedonia is a core symptom of major depressive disorder (MDD) resulting from maladaptive reward processing. Electroconvulsive therapy (ECT) is an effective treatment for patients with MDD. No previous neuroimaging studies have taken a dimensional approach to assess whether ECT-induced volume changes are specifically related to improvements in anhedonia and positive valence emotional constructs. We aimed to assess the relationship between ECT-induced brain volumetric changes and improvement in anhedonia and reward processing in patients with MDD.We evaluated 15 patients with MDD before and after ECT. We used magnetic resonance imaging, clinical scales (i.e., Quick Inventory of Depressive Symptomatology for syndromal depression severity and Snaith-Hamilton Pleasure Scale for anhedonia) and the Temporal Experience of Pleasure Scale for anticipatory and consummatory experiences of pleasure. We identified 5 regions of interest within the reward circuit and a 6th control region relevant for MDD but not core to the reward system (Brodmann Area 25).Anhedonia, anticipatory and consummatory reward processing improved after ECT. Volume increases within the right reward system separated anhedonia responders and non-responders. Improvement in anticipatory (but not consummatory) reward correlated with increases in volume in hippocampus, amygdala, ventral tegmental area and nucleus accumbens.We evaluated a modest sample size of patients with concurrent pharmacological treatment using a subjective psychometric assessment.We highlight the importance of a dimensional and circuit-based approach to understanding target engagement and the mechanism of action of ECT, with the goal to define symptom- and circuit-specific response biomarkers for device neuromodulation therapies.

The clothing industry has a reputation to operate unethical and unsustainable. Clothing companies are familiar with the issue, but the obstacles are numerous. On the ground of this, coopetition strategies can be the soulution towards a beneficial result. Coopetition strategies is when there is a collaboration between competitors, and the goal of the strategy is fix a common problem that the companies are struggling with. The thesis seeks a beneficial sustainable balance when collaborating with competitors in the clothing industry. The findings and evidence, results in a qualitative method. Five case companies are interviewed, while there was seven interviewees that participated in a semi-structured interview. As a result, the case companies do not want to take charge and lead a coopetition strategy, but all the case companies is willing and seeking a collaboration. Coopetition strategies may be a possible solution for a beneficial outcome, if the companies are on the same page, the actions are done right, and a mutual trust is involved.

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that is used for treating various neurological disorders such as major depressive disorder. TMS has been gaining popularity in the field of neurostimulation of the cerebellum, since the cerebellum is a complex structure connected with almost the entire central nervous system and TMS has promise for non-invasively probing cerebellar function. Recent studies have discovered that the cerebellum plays an important role not only in motor planning and behavior but also in the cognitive domain. However, few studies have explored how different coil designs and anatomical variations affect the effectiveness of cerebellar TMS. Therefore, in this paper, we investigated the effects of cerebellar TMS with different coil designs positioning on several locations. Finite-element modeling was conducted with Figure-8 coil and D-B80 coil. Each coil was positioned in the center, 1 and 3 cm to the left of center of the cerebellum, and all the locations were tangential to the scalp at a distance of 5 mm. Furthermore, 50 MRI derived head models were used in the computer modeling to examine how anatomical variations affect the distribution and intensity of electric field in cerebellar TMS.

This study attempts to analyze the potential impact of bilateral free trade agreements between South Korea and the members of the projected mega-RTAs such as RCEP, TPP and FTAAP under negotiation. In explaining bilateral trade flows, an augmented gravity model is constructed between South Korea and the 23 member countries. The regression result in this study shows that the traditional findings from the gravity model study are confirmed but in slightly different way. The GDP of partner country has a stronger positive influence on bilateral trade flows than that of Korea. The distance has a lesser effect than previous studies do. FTA dummies except for FTAs with Chile and Peru turn out to be insignificant in trade creation from those agreements. It seems mainly because FTA history matters or effective years of FTAs studied are not long enough to reflect some level of significance in creating trade for the countries involved.

The capacity of the Denver Basin to store CO2 in hydrocarbon reservoirs was analyzed using two techniques. The first approach employed by the Southwest Carbon Partnership assumes CO2 is injected into depleted hydrocarbon reservoirs but no fluids are withdrawn. The second method analyzes the storage capacity of the Denver Basin assuming CO2 is injected until the pressure in each oil reservoir reaches the hydrostatic gradient, and CO2 then continues to be injected into the oil reservoirs in order to recover additional oil, until the incremental oil recovery would no longer be commercially viable. The amount of CO2 sequestered in the 30 oil fields studied was found to be 160 Mt with the first method but only 50 to 70 Mt using the second method. If the CO2 source is fermentation emissions available from corn ethanol plants in Nebraska, and the produced bio-CO2-EOR oil is refined into gasoline that is consumed in Colorado, then the CO2 sequestration project described in this paper could reduce the GHG emissions from the transportation sector in Colorado by 10% during peak oil production from the project.

With the proliferation of distributed energy resources and advanced metering, modern electric power distribution systems require more simulation and engineering analysis to ensure that the planning and operation of the evolving feeders are efficient and reliable. Although distribution analytical and operational tools are widely available, their usage by utility engineers has been particularly difficult because of the huge effort required in massaging the data available from their enterprise systems into the unique database requirements for each analytical tool. This paper presents a data modelling and application usage framework for utilities that utilizes the Common Information Model (CIM) to standardize and integrate data directly available from the utility enterprise database. The paper describes this framework’s approach in standardizing a utility’s distribution data and storing it in a large database of high fidelity CIM models which can then be used as input to any analytical tool that can accept data in a CIM structure. This is demonstrated by using this CIM-based integration framework for Avista Corporation to translate data in the CIM structure into a distribution model of GridLAB-D, which is an open source distribution system simulator. The results from GridLAB-D are presented to show that many proprietary distribution analytical and operational tools can be made inter-operable if the utilities adopt such a CIM based data platform as a standard for distribution data.

A critical function in outage management for distribution systems is to quickly detect a fault and identify the activated protective device(s). With ongoing smart grid development, numerous smart meters and fault indicators with communication capabilities provide an opportunity for accurate and efficient outage management. Using the available data, this paper proposes a new multiple-hypothesis method for identification of the faulted section on a feeder or lateral. Credibility of the multiple hypotheses is determined using the available evidence from these devices. The proposed methodology is able to handle i) multiple faults, ii) protection miscoordination, and iii) missing outage reports from smart meters and fault indicators. For each hypothesis, an optimization method based on integer programming is proposed to determine the most credible actuated protective device(s) and faulted line section(s). Simulation results based on the distribution feeders of Avista Utilities serving Pullman, WA, validate the effectiveness of the proposed approach.

Transcranial magnetic stimulation (TMS) is a tool for neuromodulation that uses a time-varying magnetic field to stimulate the brain via an induced electric field (E-Field). Clinical data from Premier Psychiatric Research Institute on repetitive TMS (rTMS) for the treatment of depression shows that patients older than 55 years respond to deep rTMS with better efficacy than younger patients. Brain volume shrinks with age in adults older than 40 years, increasing the distance between their brain and scalp. In this paper, we have investigated how the induced E-Field from TMS is affected by brain–scalp distance (BSD). We have developed heterogeneous head models from MRI data of 50 subjects and created simplified head models using concentric spheres. Using finite-element analysis, we simulated TMS on these models to test the role of BSD in determining the strength and distribution of the E-Field.

Objective: The selection of a bitemporal (BT) or right unilateral (RUL) electrode placement affects the efficacy and side effects of ECT. Previous studies have not entirely described the neurobiological underpinnings of such differential effects. Recent neuroimaging research on gray matter volumes is contributing to our understanding of the mechanism of action of ECT and could clarify the differential mechanisms of BT and RUL ECT. Methods: To assess the whole-brain gray matter volumetric changes observed after treating patients with treatment-resistant depression with BT or RUL ECT, the authors used MRI to assess 24 study subjects with treatment-resistant depression (bifrontotemporal ECT, N=12; RUL ECT, N=12) at two time points (before the first ECT session and after ECT completion). Results: Study subjects receiving BT ECT showed gray matter volume increases in the bilateral limbic system, but subjects treated with RUL ECT showed gray matter volume increases limited to the right hemisphere. The authors observed significant differences between the two groups in midtemporal and subcortical limbic structures in the left hemisphere. Conclusions: These findings highlight that ECT-induced gray matter volume increases may be specifically observed in the stimulated hemispheres. The authors suggest that electrode placement may relevantly contribute to the development of personalized ECT protocols.

Objective To investigate inter-subject variability with respect to cerebrospinal fluid thickness and brain-scalp distance, and to investigate intra-subject variability with different coil orientations. Methods Simulations of the induced electric field (E-Field) using a figure-8 coil over the vertex were conducted on 50 unique head models and varying orientations on 25 models. Metrics exploring stimulation intensity, spread, and localization were used to describe inter-subject variability and effects of non-brain anatomy. Results Both brain-scalp distance and CSF thickness were correlated with weaker stimulation intensity and greater spread. Coil rotations show that for the dorsal portion of the stimulated brain, E-Field intensities are highest when the anterior-posterior axis of the coil is perpendicular to the longitudinal fissure, but highest for the medial portion of the stimulated brain when the coil is oriented parallel to the longitudinal fissure. Conclusions Normal anatomical variation in healthy individuals leads to significant differences in the site of TMS, the intensity, and the spread. These variables are generally neglected but could explain significant variability in basic and clinical studies. Significance This is the first work to show how brain-scalp distance and cerebrospinal fluid thickness influence focality, and to show the disassociation between dorsal and medial TMS.

Transcranial Magnetic Stimulation (TMS) has been gaining popularity for the treatment of Major Depressive Disorder (MDD) due to its non-invasive, painless and out-patient nature[1]. It also under investigation as a therapeutic tool for treating other psychiatric and neurological disorders such migraines, Schizophrenia, Parkinson's disease, and Post Traumatic Stress Disorder (PTSD). TMS is based on the principal of Faraday's law in which a large amount of current is passed through coils to generate time varying magnetic fields, thus inducing electric fields in the brain. There are several coils commercially available for both clinical and research studies which provide stimulation profiles that are characteristically unique in both stimulation intensity and focality. Understanding how stimulation characteristics differ between coils is important for researchers and clinicians as they attempt to choose a coil whose stimulation profile is best for a specific use case. Differences in coils have been characterized in detail in both spherical models, and in a single heterogeneous head model, but never with a population-based modeling approach [2], [3]. It is well known within the TMS community that anatomical variability, including brain-scalp distance, cerebrospinal fluid, and gyral anatomy, exists between individuals and thus contributes to varying stimulation profiles[4–6]. Population-based modeling approaches that utilize many head models, can illustrate the effects of this anatomical variability in order to see group average stimulation characteristics. Here, we use population-based modeling with 50 unique, heterogeneous head models to calculate the induced electric field in TMS from 15 coil designs. The models used in this study were taken from the Population Head Model repository [5], and contain anatomical components for skin, skull, cerebrospinal fluid, grey matter, white matter, cerebellum, and ventricles. Simulations utilizing low-frequency magneto-quasi-static solvers were used in SEMCAD X to calculate the induced electric field from various coil designs. Parameters were calculated in post-processing describing stimulation intensity (both in brain and scalp), spread (both surface and volumetric), and “hot spot” location are used to illustrate similarities and differences between these coils. Figure 1 illustrates four coils positioned on the vertex of a MRI derived head model. In this study, simulations were ranboth over the vertex and dorsolateral prefrontal cortex for all subjects and all coil designs to give perspective from two different locations of stimulation. The results described in this study will serve as a guide for both researchers and clinicians wanting to understand the differences between coils stimulation profiles.

This paper describes method to measure and calculate speed, time dilation, and length contraction of the source through using the observed differences in the vector of a ray compared to the vector of a solid projectile emanating from the same source, aimed in the same direction. This method can be used to measure motion even in absence of a reference body and has identified an inertial reference frame that has properties unlike any others. This contradicts the principle of relativity.

Niemann–Pick type C (NPC) disease is a genetic disorder associated with intracellular cholesterol accumulation in the brain and other organs, and neurodegeneration is generally believed to be the fatal cause of the disease. In view of the emerging role of matrix metalloproteinase-12 (MMP-12) in neuronal injury, we investigated its expression and potential roles in axonal degeneration in Npc1 −/− mouse brain. Microarray and quantitative real-time reversed transcription PCR analysis indicated a marked increase in MMP-12 mRNA levels in cerebellum of 3 week-old Npc1 −/− mice, as compared to wild-type littermates. Western blots showed that the ratio of mature MMP-12 over pro-MMP-12 was significantly increased in cerebellum of Npc1 −/−, as compared to wild-type mice. Immunohistochemical studies confirmed that MMP-12 expression was increased, especially in the cell bodies of Purkinje neurons in Npc1 −/− mice. Neuritic growth was significantly reduced by Npc1 siRNA knockdown in nerve growth factor-differentiated PC-12 cells, and this effect was completely reversed by treatment with an MMP-12 specific inhibitor. Furthermore, in vivo experiments showed that chronic treatment with the MMP-12 inhibitor ameliorated Npc1 deficiency-induced axonal pathology in the striatum. Our results indicate that abnormal neuronal expression of MMP-12 may contribute to axonal degeneration in NPC disease, thus providing a potential novel target for treatment.

Sleep abnormalities are extremely common in anxiety disorders and may contribute to their development and persistence. Their shared pathophysiological mechanisms could thus serve as biomarkers or targets for novel therapeutics. Individuals with Primary Insomnia were age- and sex-matched to controls and to persons with Generalized Anxiety Disorder. All underwent fMRI resting-state scans at 3-T. In Primary Insomnia and controls, sleep was recorded for 2 weeks using diaries and actigraphy. All participants completed state-anxiety and neuroticism inventories. Whole-brain connectivity of 6 fear- and extinction-related seeds were compared between the 3 groups using ANOVA. The only significant between-group main effect was seen for connectivity between the left amygdala seed and a bilateral cluster in the rostral anterior cingulate cortex. The latter is believed to exert top-down control over amygdala activity and their interaction may thus constitute an emotion regulatory circuit. This connectivity was significantly greatest in controls while Primary Insomnia was intermediate between that of controls and Generalized Anxiety Disorder. Across Primary Insomnia and control subjects, mean connectivity decreased with poorer sleep. Across all 3 groups, connectivity decreased with greater neuroticism and pre-scan anxiety. Decreased top-down control of the amygdala may increase risk of developing an anxiety disorder with preexisting Primary Insomnia.

In this chapter, we introduce the standard spike wrangling techniques that any neuroscientist should be familiar with. Specifically, we illustrate how to build programs that can analyze and display the information contained in spike trains. We start by showing how to represent and graph the spiking activity of a single neuron in a single spike train, then build toward creating a raster plot that depicts the spiking information of a single neuron over multiple trials. From there, we develop another useful representation of the information in a spike train, the peri-stimulus time histogram (or PSTH). We also cover how to compute latency to first spike and how to represent this joint information as a heat map. Throughout, we use this simple, but highly relevant, example from neuroscience to illustrate key concepts in programming, such as the perils of hard coding or the use of for loops.

In this chapter, we go beyond the time series analyses we explored in the last two chapters and introduce signal processing in the frequency domain. To get to the frequency domain, we use the Fourier transform. In the process, we aim to demystify the Fourier transform and discuss the merits of a frequency space representation of periodic signals. We cover basic signal processing issues such as sampling, Nyquist frequencies, and filtering, as well as performing an analysis of spectral power. We do this by analyzing sound signals, and applying what we learned to an example of neural data from analog signals, in this case local field potentials.