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Instructionsproject 1 Understanding Investigative Parametersno Directly Quote
September 2, 2022 /in Uncategorized /by Karis
Project #1 – Understanding Investigative Parameters
No directly quoted material may be used in this project paper.
Resources should be summarized or paraphrased with appropriate in-text and Resource page citations.
Scenario Characters:
You: Information Security Analyst, Provincial Worldwide
Ms. Carol McPherson: Information Security Director, Provincial Worldwide (Your supervisor)
Mr. Harold Newman: Human Resources Director, Provincial Worldwide
Mr. John Belcamp: (former) engineer, Product Development Division, Provincial Worldwide
Ms. Evelyn Bass: Product Engineering Manager; Product Development Division, Provincial Worldwide (John Belcamp's Supervisor)
**Characters will carry through Project 1, 2 and the Final Project. However, please remain conscious of who you are/what roll you play in EACH project and in regards to specific questions.
For the purposes of this project, imagine you are a Corporate Security Analyst, an employee of Provincial Worldwide and assigned to the company's Corporate Protection Team.
In this case, you have been notified by Mr. Newman, Human Resources Director for Provincial Worldwide, that the company has just terminated Mr. John Belcamp, a former engineer in the company's New Products Division, for cause (consistent tardiness and absences from work). Mr. Newman tells you that during Mr. Belcamp's exit interview earlier that day, the terminated employee made several strange statements that seem to elude to a current program the company is working on.
Mr. Belcamp's statements made Mr. Newman fear he might be taking Provincial's intellectual property with him to his new employer (undoubtedly a competitor). In particular, Mr. Newman is worried about the loss of the source code for "Product X," which the company is counting on to earn millions in revenue over the next several years. Mr. Newman provides you a copy of the source code to use in your investigation. Lastly, Mr. Newman tells you to remember that the Company wants to retain the option to refer the investigation to law enforcement in the future, so anything you do should be with thought about later potential admissibility in court. He tells you that in a conversation with other Corporate executives that their understanding of the investigative technological issues and how they have anything to do with a person's right as an employee seem a bit lacking; so you will need to be detailed in any explanation.
The Fourth Amendment to the U.S. Constitution reads, "The right of the people to be secure in their persons, houses, papers, and effects, against unreasonable searches and seizures, shall not be violated, and no warrants shall issue, but upon probable cause, supported by oath or affirmation, and particularly describing the place to be searched, and the persons or things to be seized." While the Fourth Amendment is most commonly interpreted to only affect/restrict governmental power (e.g., law enforcement), the fact that a formal criminal investigation is a possibility (and the Company has no desire to be named in a civil lawsuit) means you must consider its effect to your actions.
With the above scenario in mind, thoroughly answer the following questions (in paragraph format, properly referring to and citing materials used in this course as well as outside research, where appropriate, and within a reference page at the end of the project paper).
1. Prior to any incident happening, it is important for any company to implement a "forensic readiness" plan. Discuss the benefits of a forensic readiness plan and name what you believe are the top two (2) requirements to establish forensic readiness within a private sector business like Provincial Worldwide. Support your answers. (Please note that while cyber security and digital forensics have overlaps in incident response preparation, please limit your answers here to forensic readiness in the digital forensic arena, not cyber security.)
2. Ms. McPherson, out of concern for the theft/sharing of the "Product X" source code, and after discussing the issue with one of the Corporate attorneys is requesting that you and Ms. Bass start searching the areas in which Mr. Belcamp had access within the building. Can you or Ms. Bass search Mr. Belcamp's assigned locker in the Company's on-site gym for digital evidence, and why? Additionally, can you or Ms. Bass use a master key to search Mr. Belcamp's locked desk for digital evidence, whether still on site, or after Mr. Belcamp has left the premises? Support your answer.
3. A check with security confirms that John Belcamp passed through the security checkpoint when coming in to work in his vehicle. A sign at the checkpoint states that the purpose of the checkpoint is for security staff to check for weapons or other materials that may be detrimental to the working environment and employee safety. Screening is sometimes casual and usually consists of verification of an employee's Company ID card. Can security staff at this checkpoint be directed to open Mr. Belcamp's briefcase and seize any potential digital evidence, why or why not? Support your answer.
4. There is a page in the Company's "Employee Handbook" that states that anything brought onto the Company's property, including the employees themselves, are subject to random search for items belonging to Provincial Worldwide. There is a space for the employee to acknowledge receipt of this notice. Mr. Belcamp has a copy of the handbook but never signed the receipt page. Does that matter; why or why not? Explain.
5. The police have not been called or involved yet, however, Mr. Newman asks if involving the police will change your incident response. Describe how you will respond to her concerning the parameters of search and seizure, and if it will change by involving the police in the investigation at this time. Support your answer.
6. You know as an Information Security Analyst that it is important to document the details of your investigation if the company wants to insure admissibility of any evidence collected in the future. However, Mr. Newman or Ms. Bass have never heard of the term "chain of custody." How would you explain what chain of custody means, why it is important, and what could occur if the chain of custody is not documented. Support your answer.
• Each question should be answered thoroughly looking at all the issues presented, so do your research, be specific, be detailed, and demonstrate your knowledge; submitting your project through the appropriate assignment folder.
• This project should be submitted in a single Microsoft Word document (.DOC/.DOCX), with answers separated and/or numbered in respect to the question, so as to make it clear which question is being answered. It may be in a question and answer format, or as described with answers to the associated question numbers;
• The paper should be written in third-person grammar, not first person (which means – I, me, myself, etc.);
• The submission is to have a cover page that includes course number, course title, title of paper, student's name, and the date of submission per APA writing format;
• Format: 12-point font, double-space, one-inch margins;
• It is mandatory that you do some research, and utilize outside resources! You must have a reference page at the end of your project that is consistent with APA citation style and format (see https://owl.english.purdue.edu/owl/resource/560/01/ for help).
Some helpful links the professor provided
https://www.edrm.net/glossary/chain-of-custody/
https://www.youtube.com/watch?time_continue=8&v=vJdME6vczeo
https://www.youtube.com/watch?time_continue=2&v=-YKGVL4FQ24
https://www.youtube.com/watch?v=8NlyOFgFvh8
http://starsessay.com/wp-content/uploads/2022/07/logoi-300x75.png 0 0 Karis http://starsessay.com/wp-content/uploads/2022/07/logoi-300x75.png Karis2022-09-02 22:07:592022-12-18 09:36:32Instructionsproject 1 Understanding Investigative Parametersno Directly Quote
Need An Argumentative Essay On The Soccer Team Needs To Be 4 Pages Please No... His Week We Looked At What A Function Is And Various Operations And Properties...


I've been doing a lot of content audits lately. Boy are they an eye opener! When you have to sit down and read a slew of content from one vendor in a short timeframe, it can be exhausting. But I always learn a lot of great stuff from the immersion.
I was reading a great post by David Brock this morning, "But we gave them every thing they wanted!?!" and it really brought home the point of how we can diminish our opportunities by requesting too much effort from our prospective customers.
One of the core principles I've rallied around for a long time is the need to simplify effort. In fact, it's one of five of what I call Catch Factors that I've written about since 2008. It's one of those things that marketers remain blissfully unaware of unless they subject themselves to the marketing process they expect their prospects to embrace...or do a deep-dive content audit.
During the three audits I'm conducting at the moment, I've found numerous things that I've earmarked for improvement. But, today, I'd like to share three elements that make your content too much effort to deal with.
This is a common mistake that writers often make during a first draft. When you're not quite sure how to say something, you try it out in a variety of ways. The problem is that if you don't clean it up, you'll exhaust your reader. They're just looking for a reason to abandon your content. Make it too difficult for them to slog their way through to the good part (Assuming there is a good part.) and they're gone in a click.
I can't tell you how many content assets start out great to only rapidly deteriorate into the equivalent of a solution brief. This is especially true in content labeled as white papers, for some reason.
I'm on a roll, reading a great line of reasoning for why a problem must be solved and then a jolting leap is made to showcase the solution—complete with company and product names, trademarks, etc. Whoa! Stops me in my tracks. It's like the writer made the assumption that two pages of rhetoric bought them the right to shove 6 pages of product information in front of me.
Unless I'm a late-stage buyer looking for that type of information, you've missed the mark. But, the other risk you take is on not delivering on the expectations you set at the start. If your white paper is actually a solution brief but the title and summary promised thought leadership on a topic, you've disappointed your reader. Sometimes fatally.
Whether on a web page or in a white paper, I'm pretty sure that your company's branding is highly visible. In other words, your buyers know who's producing the content. It is not necessary to beat them over the head.
If you are discussing a problem that's on your buyer's priority list and following with expertise about how to solve it, do you really think the reader will think you're talking about someone else's solution even if you don't mention your product name?
Recent IDG research found that one of the biggest challenges for IT buyers was in finding content free from vendor bias.
By talking about the solution without using product names, you're more able to achieve the "illusiion" of less bias and more expertise. By sticking to the reasons why the problem should be solved and the value of doing so, you present your reader with the opportunity to consider your ideas without the impression that you're pitching the sale.
Buyers are not stupid. If what you say resonates and they want to learn more, they'll visit your website product/solution pages. You can even link to them from the paper to reduce that effort. Just do it subtly.
The point is to use your content to help position how buyers think about solving the problem by criteria that (amazingly) matches up to your solution when they go check it out.
When talking about solutions, we often draw comparisons to experiences or motifs that establish common ground. Sports, factories, space flights, the Wild West, cooking recipes, and other metaphors and analogies are incorporated into content because they're memorable and help us to help our readers connect the dots.
The precise problem that happens when we repurpose content and keep those metaphors is that they're memorable. Even with a new title and some new information, if an analogy is remembered, the prospect will assume they've read the content before and discard it. If this happens too many times, they'll discount your content as a valuable resource.
The same is true if you always discuss the challenges or problems your prospect is addressing in the same ways. Marketers must continuously think of new ways to approach the problem to create new takeaways and memories that motivate their prospects to discuss your ideas with others involved in the purchase.
Repurposing content is a good thing. Just pay attention to what gets repeated.
When's the last time you audited your content?
Seriously. Sit down and start reading. It's amazing what can become clear to you when you immerse yourself in your own content instead of only thinking about one piece at a time.
When you're doing this, try to determine what question each content asset is answering and for whom. It can be an eye opener!
The 2012 Customer Engagement Study, conducted by IDG Enterprise and released at the end of September, focused on learning more about the role content plays in an IT Decision Maker's buying process.
When I first read this, I nodded my head and thought, yes, this justifies the need for increasing the volume of content, as well as the quality of that content. But then I wondered how many of those assets were sourced from the vendor they decided to buy from? Or, at least referenced the vendor, as would be the case with an analyst report such as Gartner's Magic Quadrant Reports or other vendor analysis.
Don't just stop at the number 10.
10 content assets is reflective of one buyer. In many of my client projects we've identified 3 - 5 different stakeholders (personas) that must be educated and persuaded across the buying process. That's a total of 30 to 50 pieces of content. It's also 3 different focused "stories." So there's work to be done.
This is great to know, but if you wait until you see a prospect access 5 pieces of content from your website, have you waited too long? Unless you're certain that all content on the subject consumes is produced by your company, then this isn't awfully helpful except to give content increasing credit for influence - which we all know it has, if it's designed for the buyer in question.
1. Buyers are willing to receive follow-up content related to what they've already downloaded. And they want up to two pieces within 4 weeks of the original download.
Even better: "Only 20% of respondents said that they do not notice when content is delivered relating to search or previous downloads."
Note that Case studies can be used beginning, middle, and end and that feature articles and how-to information also play a bigger role. It's not just heavy-duty content, such as white papers. Overall, a variety of content is needed across the course of buying. It's the topical progression that must be considered to generate movement and ongoing engagement.


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Acinetobacter Found Growing in Nearly Half of Infected Patient Rooms
Multidrug-resistant Acinetobacter baumannii (MDR-AB) was found in the environment of 48 percent of the rooms of patients colonized or infected with the pathogen, according to a new study published in the November issue of the American Journal of Infection Control.
The study examined how frequently the environment surrounding the patient becomes contaminated and which environmental surfaces are most commonly contaminated.
A team of researchers from the University of Maryland School of Medicine took samples from ten surfaces in each of 50 rooms inhabited by patients with a recent (less than two months prior to environmental sampling) or remote (more than two months) history of MDR-AB. Surfaces sampled included the door knob, bedrails, bedside table, vital sign monitor touchpad, nurse call button, sink, supply cart drawer handles, infusion pump, ventilator surface touch pad, as well as the floor on both sides of the patients bed. Of these, 9.8 percent of surface samples representing 48 percent of the tested rooms showed environmental growth of A. baumannii.
Further, the study found that patients with a recent history of MDR-AB colonization or infection were not significantly more likely than those with a remote history of MDR-AB to contaminate their environment.
The authors note several potential limitations including small sample size, lack of a comparison group, and the inability to determine which came first: environmental contamination or patient colonization/infection. In addition, the study did not evaluate healthcare worker or patient movement and therefore cannot demonstrate transmission of Acinetobacter baumannii to patients as a result of environmental contamination.
Since the study was conducted, new strategies to reduce transmission of the pathogen have resulted in a significant decrease in infections and acquisition.
The research found that supply cart drawer handles (20 percent), floors (16 percent), infusion pumps (14 percent), ventilator touchpads (11.4 percent) and bedrails (10.2 percent) were most commonly contaminated, and 85 percent of environmental cultures matched the strain of the infected patient in that room. These results are of particular concern due to the frequency with which healthcare workers may touch infected surfaces during patient care.
For patients with MDR-AB, the surrounding environment is frequently contaminated, even among patients with a remote history of MDR-AB, conclude the authors. In addition, surfaces often touched by healthcare workers during routine patient care are commonly contaminated and may be a source of nosocomial transmission. The results of this study are consistent with studies of other important hospital pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and Clostridium difficile.
Acinetobacter baumannii is a species of gram-negative, multidrug resistant bacteria that has caused outbreaks of infection in healthcare facilities over the last decade and considerable concern in the medical community. Infections from this pathogen primarily occur in very ill, wounded or immunocompromised patients. The germ is capable of surviving on surfaces for prolonged periods of time, making it harder to eradicate.

redpajama_set_name: RedPajamaCommonCrawl


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HomeInternationalWhat are school uniforms like overseas?
What are school uniforms like overseas?
Sally Jones investigates the role of school uniforms at British international schools
Tracy Shand
In most British independent schools, uniform is taken for granted, be it the bog-standard white shirt and navy blazer, the eye-catching boaters, top hats, tails, canes and morning suits favoured by Harrow and Eton, the burgundy knickerbockers and mustard jumpers of Hill House, Knightsbridge, or the historic Tudor-style garb of Christ's Hospital. In most overseas schools, however, uniform is unheard of. Only Japan has an entirely individual schoolwear tradition, with all pupils resplendent in sailor suits, while Poland is currently debating the introduction of uniform throughout its state schools.
The major exceptions to the mufti habit, however, are the UK-influenced international schools overseas, including offshoots of great British establishments like Dulwich, Malvern and Repton, in far-flung outposts from Malaysia to Mongolia. Here the historic scholastic traditions of the Old Country are highly prized, particularly the striking school uniforms which symbolise for both expats and local parents the way this blue chip education sets its offspring apart from the competition.
Although the garments themselves are mostly made in the Far East, the supply of uniforms to major international schools around the world is a homegrown success story. Britain dominates this rapidly expanding market with top firms such as Norfolk-based Schoolwear International sourcing and supplying a huge range of clothing to hundreds of schools worldwide, from tiny orders of boaters crafted by specialist firms, to uniform staples such as shirts, blouses and blazers made in their millions by famous manufacturers like Banner and Rowlinson.
"School uniform is utterly different from fashion and fly-by-night suppliers usually get it wrong as it must be durable, well-designed and of really consistent quality," said Graham Michelli, MD of Schoolwear International. "Take the flagship item, a blazer. This must fit well and look immaculate on Speech Day as it's helping to set the entire tone of the school and establish its distinctive brand. But it also has to act as a goalpost at break time without coming apart at the seams – quite a tall order. I always pray that a school doesn't come to us demanding a 'Star Trek-type' uniform as the tried and tested styles, solidly made in perfect materials for the local climate invariably last far better than anything gimmicky or poorly-manufactured."
"These days most ordering is done online and good service is vital. When you're supplying a school somewhere remote like Mahe in the Seychelles, it's crucial we provide exactly the right numbers and sizes of garments really promptly as it's so expensive to send replacements," added Graham.
For Colin Bell, CEO of COBIS, the professionalism of the supplier is as crucial as the quality of the uniform itself.
"We visit hundreds of schools each year to assess them on a range of areas," he explained. "A smart, carefully designed uniform reflects the atmosphere of the school and local conditions – something the outstanding suppliers understand. In Norway and Ulaanbaatar, Mongolia, for example, daylight is at a premium so hi-vis reflective patches are built into school bags and coats. The overseas international schools all want to replicate top British uniforms but some get it wrong with certain pupils in hot Middle Eastern countries still sweltering in thick woollen blazers. A good supplier would ensure the uniform was comfortable and fit for purpose, even in extremes of climate."
The British International School of Stavanger is the only one in Norway with a uniform. Although the freedom for Norwegian children to choose their own schoolwear is a cherished right in the rest of the country, Principal Anne Howells is convinced that both school and pupils reap huge benefits from the distinctive, high-quality outfits.
"Norwegian children and parents often tell us the clothes they wear at school are a source of peer pressure and bullying," she explained. "Our incidence of bullying is extremely low and never linked to wearing the latest fashion trends. Uniform also gives the student a strong sense of identity; helps us forge a collegiate atmosphere and reinforces our school's ethos. We proudly stand out in the national schoolchildren's parade held in all Norwegian cities on 17 May."
No wonder growing numbers of international schools are developing the uniform habit.


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College marks start of building work on new Institute of Technology
The symbolic event marks the start of work on the construction of a new Institute of Technology at the college's Beverley campus. It is part of the Yorkshire and Humber Institute of Technology, one of only 12 such institutes across the country.
The project has been supported with nearly £500,000 from the Government's Local Growth Fund, secured by the Humber LEP and part of the Government's commitment to the Northern Powerhouse.
Mike Welsh, principal at East Riding College, said: "I am extremely pleased to be able to mark the start of a brand-new phase of development at East Riding College during Colleges Week. It is part of the high-profile Government investment in an Institute of Technology for Yorkshire and the Humber, and we have worked with college and university partners from across the region to make this happen. What it means is a substantial investment in higher-level technical engineering and construction skills locally, where they are needed, to fill skills gaps and provide employers with the skilled workforce they need to drive our economic recovery."
Gill Alton, group CEO of the TEC Partnership, of which East Riding College is part, said: "Our aim is to ensure that all of our students, regardless of location, age or circumstance are given the opportunities they deserve – including entering the jobs market equipped with the skills they need to achieve their ambitions. Never has this been more important, as colleges will play a significant role in helping our communities to recover from the impact of the pandemic."
The Yorkshire and Humber IoT brings investment of about £12 million of capital funding into the region, which will be invested in industry-standard equipment and facilities to provide higher-level technical training. Part of the £2.1m investment at East Riding College will fund an extension to its Flemingate campus, housing specialist training facilities for engineering.
Gemma Shahjahan, director at William Birch & Sons, the selected principal contractor, said: "We're delighted to be working on such an exciting and worthwhile project with East Riding College to build part of the Yorkshire and Humber IOT. We can see the advantages that such a facility will bring to the region, and higher-level STEM training in construction, engineering and technical professions is obviously something that is close to our heart, as it brings benefits to our industry and to our region. Added to this we see the project as a real opportunity to reach out and engage students in a live and operational building project offering a fantastic learning resource."
The training boost will enhance students' employment opportunities and improve the number of suitably qualified candidates in the technical and professional jobs market.
East Riding College's IoT will develop the highly specialised skills required by employers in the engineering and construction industries, such as computer-aided design (CAD) and computer numerical controlled (CNC) skills. The new institute will also accommodate specialist stress-testing equipment to teach engineering science, such as the science of materials and structures.
Stephen Parnaby, chairman of the Humber LEP said: "We're very pleased to support this project with £469,000 from our Local Growth Fund allocation as part of the Engineering Future Growth programme. The centre will deliver a high quality curriculum for the region's students in a bespoke facility, which will replicate the requirements most needed by employers." The Yorkshire and Humber IoT has received significant levels of employer support. Digital and engineering businesses ViSR, CATCH, Skipton Building Society, GB Recruitment and ENGIE Fabricom each recognised the need for investment in education to address their wider skills shortages and signed up as employer partners. They have been involved in designing the appropriate curriculum, supported by research from the IOT's university partners, University of York St John and the University of Hull.


The Cliffs of Moher are one Irish tourist destination that can't be missed! The cliffs boast a spectacular view, and it's even better from the sea!
Disclosure: The Cliffs of Moher post includes affiliate links. This means I make a few cents if you buy an item after clicking my link.
The Cliffs of Moher have one of the best views in all of Ireland. Consequently, the cliffs are a popular tourist spot so it's best to plan on getting there early! During the summer months, the cliffs get close to 8,000 to 10,000 people visiting a day! We got there close to the opening time of 9 AM and managed to beat all of the tour buses that seemed to arrive starting at 10 AM. Getting there early meant we were able to get a bunch of pictures in without other people in the way.
You also might want to get to the cliffs early to see the sun break through the fog, clouds, and morning rain. Maybe you'll get lucky and see a rainbow like we did! After the last of the morning fog rolled off the cliffs, it left us with the most beautiful rainbow I've ever seen! If I didn't know it before, in that moment I knew we were in Ireland!
We really loved exploring the cliffs, but we noticed that the Southern Cliffs are not ideal for strollers. The Southern Cliffs have a barrier that keeps you safely away from the cliffs, but the dirt trail was tricky on strollers. To the right of the cliffs lies O'Brien's Castle. The castle entrance fee is 2 euros for adults and 1 euro for children. The lookout from the top of the castle is very small but it's worth the view. During the busy season there's a line for the view, so in case you haven't heard it enough… it's a good idea to get there early!
O'Brien's Castle on the Cliff's of Moher.
On the grounds, there's a Cliffs of Moher museum. The museum offers information about the cliffs and you can browse and learn more about the beautiful scenery of the Cliffs of Moher. Puffins are also known to visit the cliffs during certain times of the year so keep an eye out!
Make sure to bring a selfie stick and shoes that you don't mind getting wet or muddy. The main walking path along the cliffs is paved, but if you want to venture out on the fringe paths, you should prepare for mud and puddles. A lot of these walking trails had lots of puddles and mud and there was just no getting around them. Just like in any other place in Ireland, you'll want to make sure that you have a weatherproof coat or umbrella with you. Besides the visitor's center, there's no protection from the elements once you get started.
After spending the morning at the cliffs, we were hungry! There is a small restaurant and a few food vendors on the premises, but we wanted to try food from the nearby town of Doolin. We went to Gus O'Connor's Pub and enjoyed delicious fish and chips, soups, burgers and Irish stew! The food is well worth the stop. Do note that they are cash only so make sure you have some Euros!
A great way to get a different view of the Cliffs of Moher is by the sea! We took an awesome boat tour with the company Doolin2Aran Ferries in the town of Doolin just 12 minutes away from the cliffs.
We recommend the one hour boat ride because you get plenty of time to see the cliffs and enjoy it just before you get seasick. The front of the boat is best for getting some great photos! The boat is similar to a fishing boat so it's smaller, and doesn't have a restroom. Use the bathroom before you get on board! If you're easily seasick, then we recommend you skip the boat tour, because the seas can be a bit rough at times. Additionally, wear warm clothes if you go during the fall or winter months because the ocean breeze can be chilly!
Overall, we loved the Cliffs of Moher! Tourists from all over the world come to the cliffs, and it is fun to hear all sorts of languages being spoken! The park was well taken care of and had many helpful people working there. The cliffs are surrounded by plenty of farmland, and it is green everywhere you look. The views are truly panoramas you can't see anywhere else! Take plenty of pictures, and don't forget to get a selfie with puffins if you see them on the cliffs!
Get there when the cliffs open to beat tour groups.
Pay a couple of Euros to go up into O'Brien's Castle for a great view.
Wear shoes you don't mind getting wet or muddy.
Eat lunch or dinner at Gus O'Conner's Pub in Doolin.
See the cliffs from the sea!
Aw, sounds like an amazing trip!
What an amazing day! The boat ride was one of my favorite things we did on this trip!
I love Cliffs of Moher! It's a must see! Beautiful photos!
I agree, one of my favorite spots in Ireland.
What a truly incredible photo you got of the rainbow! WOW! You could sell that to National Geographic- heavenly!


We have been learning about adjectives in our homeschooling! So far this year, Gresham (2nd grade) has studied nouns, pronouns, and verbs. Adjectives proved to be a little more abstract, but a couple of hands-on activities helped quite a bit.
When we first read about adjectives in Gresham's book, he understood the concept of describing something. I asked him to describe Nolan, our pet anole lizard. He came up with "has four legs" and "has a tail" and things like that. I needed a way to help him think of an adjective as one word that describes a noun.
I cut a piece of paper in half lengthwise and then folded it accordion style. Gresham wrote the word that he would be describing at the top, and then one adjective in each section. This worked really well!
Another day, we used a touch and feel activity to practice coming up with interesting adjectives to describe things. I filled 8 paper bags with items from around the house, and Aidan and Gresham both went down the row of bags, felt what was inside each one, and then wrote down three adjectives to describe what they felt. The items I used were some feathers, a fleece glove, some jingle bells, a baby wipe, a smooth rock, a hole punch, a toy dinosaur, and a cookie cutter.
I asked Aidan (age 10) to focus on thinking of really vivid descriptive words. At fifth grade, he needs to be moving beyond basic descriptions. This activity was a great success! Something hands-on always helps break up the monotony of a grammar book, and Owen (age 4) was able to participate too by just guessing what the items were.
Great ideas! Grammaropolis.com has great songs and videos, too. Some content is for subscribers only, but you can usually find them on youtube.
This is perfect for my youngest. Thanks, Sarah!
Good activity, what do you know about adjectives?


text:
Nathalie Just
Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Denmark
Annalisa Pascarella
Institute for Calculation Applications Mauro Picone, Department of Engineering, ICT and Technology for Energy and Transport, National Research Council (CNR), Italy
Cristian Donos
University of Bucharest, Romania
METHODS article
Front. Neurosci., 14 June 2021
Sec. Brain Imaging Methods
Volume 15 - 2021 | https://doi.org/10.3389/fnins.2021.652841
MRIES: A Matlab Toolbox for Mapping the Responses to Intracranial Electrical Stimulation
Kaijia Sun1,2, Haixiang Wang3, Yunxian Bai2, Wenjing Zhou3 and Liang Wang2,4*
1School of Systems Science, Beijing Normal University, Beijing, China
2CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China
3Epilepsy Center, Tsinghua University Yuquan Hospital, Beijing, China
4Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Propose: Directed cortical responses to intracranial electrical stimulation are a good standard for mapping inter-regional direct connectivity. Cortico-cortical evoked potential (CCEP), elicited by single pulse electrical stimulation (SPES), has been widely used to map the normal and abnormal brain effective network. However, automated processing of CCEP datasets and visualization of connectivity results remain challenging for researchers and clinicians. In this study, we develop a Matlab toolbox named MRIES (Mapping the Responses to Intracranial Electrical Stimulation) to automatically process CCEP data and visualize the connectivity results.
Method: The MRIES integrates the processing pipeline of the CCEP datasets and various methods for connectivity calculation based on low- and high-frequency signals with stimulation artifacts removed. The connectivity matrices are saved in different folders for visualization. Different visualization patterns (connectivity matrix, circle map, surface map, and volume map) are also integrated to the graphical user interface (GUI), which makes it easy to intuitively display and compare different connectivity measurements. Furthermore, one sample CCEP data set collected from eight epilepsy patients is used to validate the MRIES toolbox.
Result: We show the GUI and visualization functions of MRIES using one example CCEP data that has been described in a complete tutorial. We applied this toolbox to the sample CCEP data set to investigate the direct connectivity between the medial temporal lobe and the insular cortex. We find bidirectional connectivity between MTL and insular that are consistent with the findings of previous studies.
Conclusion: MRIES has a friendly GUI and integrates the full processing pipeline of CCEP data and various visualization methods. The MRIES toolbox, tutorial, and example data can be freely downloaded. As an open-source package, MRIES is expected to improve the reproducibility of CCEP findings and facilitate clinical translation.
Mapping human brain connectivity quantitatively on a large scale has attracted increasing attention in recent years. Understanding brain connectivity enables us to explore the normal functions and dysfunctions of the brain. Numerous studies have revealed important physiological (Watrous et al., 2013; Solomon et al., 2017, 2019) and psychological evidence (van Diessen et al., 2013; Bartolomei et al., 2017; Lagarde et al., 2018) from the perspective of brain connectivity. There are many methods of probing brain connectivity, such as diffusion tensor imaging (DTI), which is used to measure anatomical connectivity, and functional magnetic resonance imaging (fMRI), a way of measuring functional connectivity. However, such neuroimaging techniques cannot quantitatively measure the information that is transferred directly between the areas. In comparison with statistical-based approaches (e.g., Granger causality) for measuring direct connectivity from the EEG or fMRI signals (Reid et al., 2019; Jafarian et al., 2020), detecting cortical responses to invasive electrical stimulation is a good standard for mapping inter-regional direct connectivity, and has been widely used in physiological (Enatsu et al., 2015, 2016; Keller et al., 2018; Usami et al., 2018; Dionisio et al., 2019) and pathological studies (David et al., 2011; van 't Klooster et al., 2011, 2017; Boido et al., 2014; Bartolomei et al., 2017; Tousseyn et al., 2017; Zhao et al., 2019).
Single pulse electrical stimulation (SPES) has been used to elicit cortical responses since 1990 (Wilson et al., 1990, 1991). The evoked potentials recorded in other cortices are termed cortico-cortical evoked potential (CCEP). CCEP provides a way to explore functional networks in the living human brain, including language system (Matsumoto et al., 2004; Keller et al., 2011; Koubeissi et al., 2012; Saito et al., 2014; Tamura et al., 2016), motor system (Matsumoto et al., 2006; Swann et al., 2012; Terada et al., 2012; Enatsu et al., 2013), and the limbic network (Almashaikhi et al., 2014; Enatsu et al., 2015; Jiménez-Jiménez et al., 2015). With regard to epilepsy, SPES has been used for two major purposes, one to detect the epileptogenic zone, and the other to probe the epileptic network during seizures (Matsumoto et al., 2017).
There are many different methods to characterize the properties of CCEP responses. For low-frequency (LF) responses, the typically evoked waves (e.g., N1/P1) are commonly used as an indicator. The amplitude and latency of the peak are considered as the direct response strength and latency (Conner et al., 2011; Keller et al., 2011; Parker et al., 2018). The root mean square (RMS) calculated from the signals after electrical stimulation is also widely used to represent the response strength (Dionisio et al., 2019; Prime et al., 2020). Recent studies have revealed high-frequency (HF) responses to electrical stimulation in remotely recorded areas. Given that the broadband gamma activity is usually proposed to reflect local neural population activity (Crone et al., 2001; Voytek et al., 2009; Wang et al., 2010), broadband gamma activity in the recorded electrodes can be used to represent the response strength evoked by electrical stimulation (van 't Klooster et al., 2011; Crowther et al., 2019).
Currently, the steps of CCEP data processing are cumbersome and time-consuming for many researchers and clinicians without programming experience. Few packages have been developing to process CCEP data and visualize the results. For example, the toolbox called FAST (Taylor et al., 2020) is mainly developed for visualizing the low-frequency responses at the channel level. However, this toolbox did not provide an integrated function including various calculation methods that were important for comparing different indicators in the same dataset. Furthermore, in clinical applications and basic research related to CCEP intuitively presenting the connectivity results in different ways is essential but unfortunately is lacking in the FAST toolbox. The traditionally and widely used toolboxes, such as EEGLAB (Delorme and Makeig, 2004) and Fieldtrip (Oostenveld et al., 2010), were developed for processing electrophysiological data and cannot be directly used for CCEP data.
In this study, we develop a Matlab toolbox named MRIES (Mapping the Responses to Intracranial Electrical Stimulation) to integrate the full pipeline of CCEP data processing and connectivity visualization methods. The users can easily complete the entire data processing in the GUI. Common visualization methods are also integrated in the GUI, which makes it easy to intuitively display and compare different indicators and visualization methods. To assess the validity of the toolbox, we applied it and explored direct connectivity between the medial temporal lobe and insular in eight epilepsy patients.
Subjects and Data Acquisition
The subjects in this study were eight patients with refractory focal epilepsy who underwent SEEG electrode implantation at the hospital. They were all implanted with SEEG electrodes to further delineate the epileptogenic zone. The clinical characteristics of eight patients are summarized in Table 1. Their age ranged from 21 to 38 years old (27.50 ± 6.12). These patients have medial temporal lobe and insular contacts: five of them have electrodes in the left hemisphere; one of them has electrodes in the right hemisphere; two of them have electrodes in both hemispheres. For analysis, we only choose the hemisphere in which there are medial temporal lobe (MTL) and insular contacts. This sample CCEP data set is used to validate the MRIES toolbox.
Table 1. Demographic information of patients for MTL-Insular connectivity analysis.
The data was acquired using a Neurofax EEG-1200 system at a sampling rate of 2,000 Hz. The electrical stimulus consisted of a constant current square wave pulse of 0.3 ms duration, the current intensity of 5 mA, and the pulse frequency of 1 Hz with alternative polarity. About fifty biphasic pulses of electrical stimulation were delivered to two neighboring contacts in each session, while the EEG signals of all electrode contacts were recorded.
Electrode Reconstruction and Selection
Post-implantation CT images were co-registered onto pre-implantation MR images using Freesurfer (v6.0.0,1). The registration was visually verified and manually adjusted if necessary. Intracranial electrodes were identified using clustering-based segmentation and classified according to anatomical landmarks in the native space (Qin et al., 2017). For visualization of all subjects' electrodes, each subject's MRI was co-registered to the MNI space. All electrodes were then superimposed onto the standard brain. The location of electrode contacts was ascertained by visual inspection by the neurologists (HXW and WJZ).
Cortical and volumetric parcellations were performed using the Desikan-Killiany atlas in Freesurfer. The insular contacts were selected based on their location within the insular itself, and the medial temporal contacts were selected based on their location in the hippocampus, amygdala, entorhinal, and parahippocampal gyrus. The numbers of ROI contacts from all patients are listed in Table 1.
MRIES Processing Procedures
MRIES is a GUI-based Matlab toolbox for Windows, Mac, and Linux operation systems and can be used without Matlab programming experience. MRIES can calculate and map the responses to either a single pulse or repeated multiple electrical stimulations, including data preprocessing, response detection, connectivity matrix construction, and various visualization methods. The required input data are: (1) the recorded data of CCEP; (2) the information file, including subject ID and electrode labels that can be manually edited in a text format; (3) pre-operative T1 and post-operative CT images; (4) brain pial and parcellation files output from FreeSurfer; (5) contact coordinates file that can be manually generated. The set of the tools are easily available by Matlab-based GUI and the open-source package is suitable for customized functions and modules. It is worth noting that all parameters mentioned below can be set flexibly in a customized way. Here, we describe the detailed procedures.
The procedures of MRIES include four steps: (1) data preprocessing; (2) response detection; (3) connectivity matrix construction; and (4) connectivity visualization (Figure 1).
Figure 1. Main procedure for pipeline processing and visualization of responses to electrical stimulation. The procedure includes four parts: (1) data preprocessing; (2) response detection of electrical stimulation; (3) cortico-cortical connectivity calculation; and (4) result visualization.
The EEG files should be in European data format (edf) so that they can be converted via the clinical EEG recording system. The file can be sorted as the rank of the electrodes, and the invalid and unavailable channels should be removed in advance. Because electrophysiological data are always recorded with high time resolution and simultaneously recorded with multiple channels, the whole CCEP data of one subject is too big to be loaded into the memory of the computer. To solve this problem, the toolbox prefers to deal with the segmented files, which consist of the partial data by grouping some contacts (e.g., dozens of stimulation contact pairs) in succession or even one single contact pair. After this step, the edf files can be separated into the different stimulated contact pairs, renamed in the order of electrodes, and transformed to mat format for the next step.
Epoching
Before this step, we used a high-pass filter (>0.1 Hz) to remove linear drift. Then, the epoching step aimed to extract and align repeated trials from the completely recorded data corresponding to the same stimulated contacts (mat file generated in the "Data input" step).
The epoching processing involved two steps, detecting stimulation onset and aligning epochs. To detect stimulation onset, in some cases the stimulation events were recorded in an independent marker channel simultaneously. At the stimulation beginning, a pulse signal will be marked in that marker channel. Thus, the peaks in the marker channel are automatically detected as stimulations and the start of peaks are detected as the stimulation onset. In other cases, in which there is no specific marker channel, one needs to detect the stimulation onset via the artifacts in the recorded contacts induced by the electrical stimulation. In this case, the user can enter the channel number to detect the stimulation and stimulation onset.
If the number of stimulations was detected correctly, the processing then went to the aligning step. Then the specific time window before and after stimulation onset was extracted as an epoch and all epochs were aligned at stimulation onset for significant response detection.
Bad-epoch removal
Bad-epoch removal was based on the variation of the different epochs. The abnormal signal (e.g., epileptic discharge) causes an obvious large voltage amplitude compared with the normal signal. We used the 3 standard deviations above the mean as a threshold to remove the epochs with abnormal signals.
Response Detection
Low-frequency response
The typical low-frequency response consisted of an early negative or positive wave (N1/P1) and a late slow wave (N2/P2). It has been proposed that the early (or late) wave reflected a direct (or indirect) connection between the recorded and simulated location. The toolbox focused on the early response (i.e., N1 or P1). The N1 denoted the first negative wave, while the P1 was the first positive wave, and the time range of N1/P1 peak onset was limited within 7–50 ms after electrical stimulation onset to avoid the stimulation artifact. The significant peak amplitude and peak latency were used to construct the connectivity matrix (Figure 2A). The root mean square (RMS) was also widely used as an indicator of the response. We calculated the RMS of the electrode j based on the averaged epoch signal x within the time window [t1t2] after stimulation onset as follows (Figure 2A).
Figure 2. Low- and high-frequency responses extracted from a single session. (A) A representative curve of low-frequency response (black line) averaged from each epoch response (gray lines). The blue triangles represent significant N1 and P1 peak response which is determined by 6 standard deviations of baseline (the two horizontal dotted lines) and in the time range from 7 to 50 ms. The RMS is calculated from 7 to 300 ms after stimulation (two green vertical dotted lines). (B) A representative curve of high-frequency response (black line), i.e., the averaged broadband gamma envelop signal over different epochs (gray lines). The variance is calculated from the averaged gamma envelop from 10 to 100 ms after electrical stimulation (two orange vertical dotted lines). The blue triangle represents high-frequency peak response. The peak latency is marked by the pink arrow.
R  M  S j = ∑ t = t 1 t 2 x t 2 | t 2 - t 1 |
High-frequency response
The electrical stimulation artifacts can make a large and false activity around the stimulation onset. However, directly removing the artifacts led to discontinuous signals which introduced new artifacts. Based on the method proposed by a recent study (Crowther et al., 2019), we replaced the artifacts with the linear merged signals before and after the stimulation, extracted the broadband gamma signal (e.g., 70–170 Hz), and then computed the absolute value of the Hilbert transform of these band-pass filtered results. In our datasets, we found that the SNR (signal-to-noise) used in Crowther's study was too strict in some response detection. Thus, instead of SNR, we used the variance as an indicator of strength. Similar to low-frequency response detection, the significant high-frequency activity and peak latency were also calculated (Figure 2B).
Connectivity Matrix Construction
Low-frequency connectivity
The low-frequency connectivity was mainly focused on response strength and latency. To detect the direct response, we chose the earlier response between N1 and P1 to perform the statistical test and extract the peak amplitude and latency as a statistical indicator of one stimulation-response pair. Given that different areas have different baseline activity, we also measured the normalized amplitude by calculating the z-score of peak amplitude by the distribution of the baseline amplitude. Thus, for one subject we can obtain the LF-amp (low-frequency amplitude), LF-lat (low-frequency latency), and LF-Zamp (low-frequency z-score amplitude) connectivity matrix. For the RMS measurement, we can obtain the LF-RMS (low-frequency RMS) connectivity matrix. We also calculated the LF-sRMS (low-frequency significant RMS) matrix by multiplying LF-RMS and binarized LF-amp.
High-frequency connectivity
We calculated the high-frequency connectivity by the p-value of the permutation test and also obtained the peak of the averaged high-gamma envelop signal. We used Bonferroni correction on the resultant p-values for multiple comparisons. For visualization, we calculated the negative log of the corrected p-values for the HF-str (high-frequency strength) connectivity matrix and the peak latency for the HF-lat (high-frequency latency) connectivity matrix. We also calculated the HF-sign (high frequency significant) connectivity matrix by multiplying HF-str and binarized HF-lat matrix.
Connectivity Visualization
Matrix visualization
Heat map visualization is a basic method of visualization. We use a two-dimensional heat map to represent the connectivity strength (e.g., RMS) evoked by stimulating two paired contacts.
Circle map visualization
We use a circle map to visualize the connectivity matrix. An anatomical atlas is required to display region information for each contact, such as the Desikan-Killiany atlas. Every node of the circle map represents one contact and the edge linking nodes represents significant connectivity and direction. The circle map offers a clear way to display the whole connectivity pattern.
Volume visualization
The implanted electrodes only sample part of the brain. To display the responses at a large scale, we made a linear interpolation of response around the electrode location to estimate the activity in the surrounding unsampled areas using the method proposed in a previous study (David et al., 2011). The MRIES toolbox can present the whole-brain interpolated responses in the individual brain.
Surface visualization
For directly displaying the connectivity and contact location in the brain surface, it is possible to show the connectivity matrix in a three-dimensional brain surface with contact locations. This method requires the brain pial and parcellation files output from FreeSurfer and contact coordination file. This visualization can intuitively display the responses in a different region.
Statistical test in response detection
Low-frequency response is detected at each time point based on the averaged signal over different epochs. The signal after the stimulation is tested at each time point. The signals after the stimulation beyond 6 standard deviations of the mean obtained from the baseline (200 ms before stimulation onset) were detected as significant time points. The significance duration was restricted, continuously lasting for more than 5 ms.
Using the method proposed by a recent study (Crowther et al., 2019), we calculated the variance of the averaged broadband gamma signal at each location between 10 and 100 ms post-stimulation. To test whether the corresponding variance value was significant, we applied a randomization test in which we repeated the variance calculation 10,000 times after reversing the broadband signals in each trial and applying a circular shift at a randomly selected interval. This produced a distribution of variance values that represented no significant modulation of broadband gamma activity in the post-stimulus period. We determined the statistical significance of post-stimulus broadband gamma changes at each electrode by applying the observed variance value to a normal cumulative distribution function calculated from the permutation distribution of log-normalized variance values for each channel. Finally, we measured the magnitude of broadband gamma modulation by calculating the negative log of the Bonferroni-corrected p-values. To establish the peak latency of the broadband gamma response, we modeled average broad-band gamma amplitudes in the 200 ms prior to a stimulus with a normal distribution and then determined the peak time after the stimulus at which the average amplitude exceeded the voltage corresponding to α = 0.001 and was the maximum within 10–100 ms.
Statistical analysis in the toolbox validation
We focus on direct connectivity between the medial temporal lobe and insular to validate the CCEP results output from the toolbox. The Binomial test was employed to determine the significance of inter-regional connectivity for each patient. Specifically, within the total connectivity (i.e., all pairs of stimulating and responding sites between two regions) we counted how many pairs are significant in the low-frequency connectivity detected by MRIES. Then using the significance level for each pair (i.e., the 6 standard deviations), we obtained the p value in the Binomial test. Finally, we reported the percentage of patients with significant connectivity between regions.
The MRIES Toolbox
The MRIES toolbox mainly included two parts, the data processing GUI (Figure 3A) and visualization GUI (Figure 3B). Before the data processing, the user needs to place the data and information files in specific folders. Then, they should press the "Subject Information" and "Parameter Setting" buttons in the data processing GUI (Figure 3A) and enter the subject, electrode, and parameter information in the newly opened window (Supplementary Figures 1, 2).
Figure 3. Main GUI of the toolbox. (A) Data processing GUI, including the processing pipeline, separate processing step, and visualization. (B) Visualization GUI. The individual brain is shown in different views. The lower right part shows the information and controllers highlighted in the color-coded box. The volume and voxel coordinates are illustrated in the blue box. The subject information is illustrated in the pink box. The electrode information is illustrated in the yellow box. The specific stimulated electrode pair and indicator illustrated in the green box can be chosen and then the responses to this electrode pair are shown in the volume space. Other visualization GUIs and 3D-electrode locations are shown in the red box.
In the data processing GUI, the toolbox can easily run the processing pipeline as described above to get a different connectivity matrix by pressing the button "Data Processing Pipeline." Alternatively, the data processing GUI can also be used separately for specific processing steps. Pressing the button "Data input" can complete the step "Data Input." Pressing the button "Epoching and Response Detection" can complete the steps "Epoching," "Bad-epoch removal," and "Response detection." Pressing the button "Connectivity matrix construction" can complete the step "Connectivity Matrix Construction." In both completely separated situations, the data will be processed automatically and the process progress will show in command after pressing this button. After the data processing, the user can press the "Visualization Interface" button to open the visualization GUI (Figure 3B). Different visualization methods are integrated into the Visualization GUI (Figure 4). In these GUIs, we can also add some controllers to display patient information and change the connectivity matrix and stimulation contacts (for volume and surface view GUI). The detailed processing steps and GUIs can be seen in the tutorial.
Figure 4. Connectivity visualization. (A) Connectivity matrix. The stimulated electrodes are shown in the y-axis and the recorded electrodes are shown in the x-axis. The color-coded numbers represent RMS values here, which depends on the selection of response indicators in the main GUI toolbox. The unstimulated pairs and recorded electrodes with a short distance (radius < 5 mm) to the stimulation pair are illustrated in white. The exampled stimulation result marked in the red box is shown in panels (C,D). (B) Circle map visualization. The number of rectangular boxes in each compartment represents the number of contacts in each region labeled aside (L = left, R = right, RosACC = rostral anterior cingulate cortex, RosMFG = rostral middle frontal gyrus, SFG = superior frontal gyrus, STG = superior temporal cortex, CauACC = cauda lanterior cingulate cortex, CauMFG = caudal middle frontal gyrus, Fronttri = parstriangularis of the inferior cortex, PCC = posterior cingulate cortex, ParaCG = paracentral gyrus, PreCG = precentral gyrus). The curves represent significant connectivities. The gradient color curves represent directional connectivity (from blue to red) and the black color curves represent bi-directional connectivity. (C) Brain response mapping is shown in individual volume space in a format of linear interpolation surrounding the implanted electrodes. The white dot indicates stimulation position. (D) Surface view. All contacts and electrode labels are shown in the 3D surface view and the color represents the RMS value. The black circle dots represent stimulation contact-pairs.
Matrix GUI
The controller "Conn Mat" in visualization GUI (Figure 3B) can open the matrix GUI. There are two parts in this GUI: the matrix visualization and control area. The matrix visualization is the heat map of the connectivity matrix (Figure 4A). Color represents the value of the connectivity matrix, and the abscissa and ordinate represent stimulation and response contacts. The control area includes the sliders, which are used to ignore the closer response contact and lower response value, and the display boxes to display the stimulation contact, response contact, and response value.
Circle Map GUI
The circle map GUI shows the circle map of the connectivity matrix described above. As shown in Figure 4B, every rectangular box in the circle represents a contact, and the region label is shown outside the circle. The curve represents significant connectivity. The gradient color curves represent direct connection and the black color curves represent the bi-direction connection.
Volume GUI
The volume GUI, integrated into the main visualization GUI (Figure 3B), includes two parts, the displaying area, and the control area. The displaying area can display the individual brain structure. After choosing specific stimulation contact and connectivity matrix, the volume visualization also can be displayed in the brain (Figure 4C). The control area can input the patient folder, choose the specific stimulation contact-pair and connectivity matrix, and open the other visualization GUI. These controllers can update the whole visualization.
Surface GUI
The surface GUI also includes the visualization area and control area. All contacts and electrode labels are shown in the surface view and the color represents the response value. The black circle dots represent stimulation contact-pairs (Figure 4D). In the control area, there are buttons that rotate the visual angle of the surface brain. The information of the stimulation contact is also displayed if contact information is input in the MRIES.
Data Organization
Each patient should have a unique folder, and the input and output files are under this folder and organized as below.
The input data consists of five parts. (1) The recorded data of CCEP converted to edf format and placed in the edf folder, and the relevant information about the edf file is entered into the file edf_match.txt. (2) Patient information: subject and electrode information are entered into the file subjectinfo.txt. (3) Reconstruction results: one can copy Freesurfer reconstruction result to the subject folder. (4) Pre-operative T1 and post-operative CT images: the two images should be co-registrated first and placed in the brain3D folder. (5) Contact coordinate file: the coordinates of contacts are saved into the file autocoordinate.mat and placed in the brain3D folder. Detailed input data organization can be seen in the tutorial.
Output Result
For each subject, the MRIES toolbox automatically generates some file folders to store the result. Specifically, the subj_elec_info.mat saves the patient and electrode information. The data folder includes the mat file of every contact pair converted from edf files, and each line of one file in data means the repeat trials recorded in the channel. Every file in the stimulationdata folder includes all response indicators from repeat trails of the same stimulation contact-pairs. The Matrix folder includes all the connectivity matrix of all kinds of indicators, which are used in the visualization GUIs. For example, "conn_matrix_LF_lat.mat" means the low-frequency latency connectivity. The detailed organization of outputs can be seen in the tutorial.
Toolbox Validation Using MTL and Insular Connectivity
All eight patients had significant connectivity from MTL to insular (all p values < 0.001, Binomial-test, Table 1). Seven of the eight patients had significant connectivity from insular to MTL (all p values < 0.001 except for patient 5, Binomial-test, Table 1). This bidirectional connectivity (Figure 5) between MTL and insular is consistent with the findings reported in previous studies (Enatsu et al., 2015; Dionisio et al., 2019).
Figure 5. Contact distributions and direct connectivity between MTL and insular, revealed by CCEP. The contacts' distributions of patients (Table 1) in MNI152 standard space (Insular, red; MTL, blue). The two black arrows indicate significant bidirectional connectivity between the insular and medial temporal lobe based on the result of this study.
The toolbox MRIES integrates the processing pipeline and visualization of cortical responses to electrical stimulation. Many measurements (e.g., low-frequency response and peak latency, RMS, high-frequency response, and peak latency) are calculated which makes it possible to compare the different results at the same time. Various visualization methods are also integrated into this GUI, which makes it intuitive when displaying a connectivity matrix constructed by different measurements.
The main advantage of MRIES is easy and convenient to use, allowing one to choose the full processing pipeline once the required data and information files are provided correctly. The remaining procedures can be completed automatically. If only part steps of the pipeline are needed, one can choose specific steps and obtain intermediate documents. The visualization controllers are also integrated into GUI and it is easy to further expand them.
Mapping cortical responses to electrical stimulation in the human brain is of great significance for clinical and scientific purposes. The electrical stimulation technique has been widely used for studying normal brain connectivity (Enatsu et al., 2016; Dionisio et al., 2019) and the influence of brain diseases on functional brain network (Kobayashi et al., 2017; Tousseyn et al., 2017; Davis et al., 2018). The existing toolboxes are not suitable for processing CCEP data and displaying the connectivity results. For example, although EEGLAB (Delorme and Makeig, 2004) and FieldTrip (Oostenveld et al., 2010) offer some functions for scalp EEG signal processing, they are not applied to CCEP data. In contrast, the FAST graph (Taylor et al., 2020) presents a new framework for calculating low-frequency responses to electrical stimulation and displays the results at the contact level. However, it remains difficult to carry out the calculations of various indicators and intuitive visualization of inter-regional connectivity. The MRIES toolbox was developed to address these issues and can be directly used for clinical doctors to probe the epileptic network during a seizure. The connectivity results calculated by MRIES can be easily pooled together over the subjects from multiple epilepsy centers, furthering understanding of functional brain organization.
In the current study, we also performed the validation of the MRIES toolbox based on the connectivity between the medial temporal lobe and insular. This connectivity has been widely studied in different ways, such as DTI (Ghaziri et al., 2018; Nomi et al., 2018), fMRI (Ambrosi et al., 2017), and meta-analytic (Cauda et al., 2012). Previous studies also used CCEP data to detect the connectivity between the limbic system and insular and found significant bidirectional connectivity between the two regions (Enatsu et al., 2015; Dionisio et al., 2019). We measured the CCEP connectivity between the two regions in eight epilepsy patients by MRIES and also found significant bidirectional connectivity. These consistent results provide the reliability of the MRIES.
There are several limitations to the toolbox. Currently, it only supports the European data format for raw CCEP data. Other data formats, such as Brain Imaging Data Structure (BIDS), will be integrated in the future. Some data processing steps are still time-consuming because of the limited speed of Matlab scripts. The parallel computing and C-language modules will be integrated into the MRIES toolbox to improve computational efficiency in the future.
In summary, the MRIES toolbox can auto-process the cortical responses to electrical stimulation, and include different visualization methods. The functions developed in the MRIES toolbox have been integrated into the GUI, which is convenient for researchers and clinicians without programming experience. The MRIES toolbox, tutorial, and one example data can be freely downloaded at GitHub2 and FigShare3. As an open-source package, MRIES is expected to improve the reproducibility of CCEP findings and facilitate clinical translation.
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s: LW, lwang@psych.ac.cn.
The studies involving human participants were reviewed and approved by Institutional Review Board of the Institute of Psychology, Chinese Academy of Sciences. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
KS and LW designed the software. KS, YB, and LW developed the software. KS, HW, and LW wrote the manuscript. HW and WZ provided the experimental data. All authors contributed to the article and approved the submitted version.
This study was supported by the National Natural Science Foundation of China (31771255 and 32020103009) and CAS Interdisciplinary Innovation Team (JCTD-2018-07).
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnins.2021.652841/full#supplementary-material
^ https://surfer.nmr.mgh.harvard.edu/
^ https://github.com/SunKaijia0065/MRIES
^ https://figshare.com/articles/dataset/MRIES_s_sample_data/14376110
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Keywords: electrical stimulation, cortico-cortical evoked potential, Epilepsy, SEEG, functional connectivity
Citation: Sun K, Wang H, Bai Y, Zhou W and Wang L (2021) MRIES: A Matlab Toolbox for Mapping the Responses to Intracranial Electrical Stimulation. Front. Neurosci. 15:652841. doi: 10.3389/fnins.2021.652841
Received: 13 January 2021; Accepted: 26 April 2021;
Nathalie Just, INRA Centre Val de Loire, France
Annalisa Pascarella, Istituto per le Applicazioni del Calcolo "Mauro Picone" (IAC), Italy
Cristian Donos, University of Bucharest, Romania
Copyright © 2021 Sun, Wang, Bai, Zhou and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Liang Wang, lwang@psych.ac.cn


text:
By AHT Administrator On Sep 30, 2015
Britain will attempt to carry out its first womb transplants after a clinical trial enabling 10 women to undergo the procedure was approved, doctors said Wednesday.
Surgeons hope to replicate the success of the world's first-ever effective womb transplant, conducted on a 36-year-old woman in Sweden who gave birth last year.
More than 100 women have been approved as potential recipients ahead of the trial which is set to start in the first half of next year, after ethical approval was granted by the Imperial College London.
The procedure has previously also been attempted in Saudi Arabia and Turkey but in both cases did not lead to live births.
Richard Smith, a consultant gynaecologist at the Queen Charlotte's and Chelsea Hospital in London, will lead a team of surgeons carrying out the trial following 19 years of research.
"There's an innate desire for many women to carry their own baby and this procedure has, potentially, the capacity to satisfy that innate desire," Smith told BBC radio.
Around one in 5,000 women is born without a womb, while others lose the organ as a result of cancer.
Smith said it was "heartrending" to meet those women affected.
Ten women will be selected for the trial subject to certain criteria being met. They must be aged 38 or under, have a long-term partner and be a healthy weight.
However surgeons currently only have funds for "one or maybe two cases" said Smith, adding that they were "desperate" for more funding to complete the £500,000 (677,000 euros, $759,000) trial.
In a six-hour operation participants will receive a womb from a donor who is classed as brain dead but whose heart is still beating.
– 'Feel baby grow inside you' –
In the transplant in Sweden, the replacement organ came from a live donor — a 61-year-old family friend of the recipient who had been through menopause seven years earlier.
The baby boy was born by Caesarean section at 31 weeks last October to a woman whose genetic condition meant she was born without a womb.
Two other transplant attempts have been reported elsewhere, but neither resulted in a live birth.
The first, carried out in Saudi Arabia in 2000, ended in failure after three months when the uterus became necrotic and had to be removed.
The second, carried out in Turkey in 2011, entailed a uterus that was transplanted from a deceased donor, resulting in a pregnancy that miscarried within six weeks.
Sophie Lewis, 31, hopes to be among the first to undergo the transplant in Britain, The Times reported.
"To be told at 16 you can't have children, and then to be given the opportunity to feel your baby grow inside you — it's too much to say no to," she told the newspaper.
Ahead of the trial, embryos will be created and frozen using each woman's eggs and sperm from her partner.
The women must take immunosuppressant drugs to prevent their body from rejecting the womb, which will be removed either six months after the birth or after the woman has had a second child.
If successful, the baby would be delivered by Caesarean section to prevent the donor womb undergoing the strain of labour.
Caesarean sectionChelsea Hospitalmmunosuppressant drugswomb transplant
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FOI compliance: ICPC rated third best among MDAs
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WHO removes Nigeria from Polio endemic countries
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text:
Joshua 3:14
So when the people set out from their tents to cross the Jordan with the priests carrying the ark of the covenant before the people,
Nave's Topical Bible - Ark; Miracles; Water; Scofield Reference Index - Israel; Miracles; Torrey's Topical Textbook - Ark of the Covenant; Jordan, the River; Miracles Wrought through Servants of God;
American Tract Society Bible Dictionary - Miracle; Bridgeway Bible Dictionary - Ark; Earthquake; Palestine; Priest; Holman Bible Dictionary - Water; Hastings' Dictionary of the Bible - Jericho; Joshua; Morrish Bible Dictionary - Jordan ; Miracles; People's Dictionary of the Bible - Ark; Chief parables and miracles in the bible; Journeyings of israel from egypt to canaan; Lachish; Smith Bible Dictionary - Tabernacle;
Condensed Biblical Cyclopedia - Conquest of Canaan; The Jewish Encyclopedia - Ark of the Covenant; Miracle;
Poor Man's Commentary
And it came to pass, when the people removed from their tents to pass over Jordan,.... Which they had pitched very near it, upon their removal from Shittim, and in which they had lodged the night past:
and the priests bearing the ark of the covenant before the people; at the distance of two thousand cubits.
Gill, John. "Commentary on Joshua 3:14". "The New John Gill Exposition of the Entire Bible". https://www.studylight.org/commentaries/geb/joshua-3.html. 1999.
Joshua 3:14 And it came to pass, when the people removed from their tents, to pass over Jordan, and the priests bearing the ark of the covenant before the people;
Ver. 14. And it came to pass.] In Joshua 3:13 it was, "And it shall come to pass." "The word of God cannot be broken"; [John 10:35] all must be fulfilled that is foretold.
Trapp, John. "Commentary on Joshua 3:14". John Trapp Complete Commentary. https://www.studylight.org/commentaries/jtc/joshua-3.html. 1865-1868.
14.And the priests bearing the ark — The word priests is the grammatical subject of the implied verb, were. [Joshua 3:14-16 should be rendered thus: And it came to pass while the people were removing from their tents to cross the Jordan, and the priests bearing the ark of the covenant were before the people, and as those bearing the ark came to the Jordan, and the feet of the priests bearing the ark were dipped in the edge of the waters, (and the Jordan was full over all its banks all the days of harvest,) then stood the waters which came down from above; they rose up, one mass, very far away, in Adam, the city which is beside Zarthan, and those [waters] which came down upon the Sea of the Wilderness, the Salt Sea, were entirely cut off, and the people crossed in front of Jericho.] 15. Overfloweth all his banks — The Jordan flows in a deep valley about three quarters of a mile wide, and about fifty feet deeper than the wide plain (the Ghor) in which it lies. In this lower valley a narrow fringe of canes, intermingled with trees, runs along the edge of the river. In the ordinary swellings of Jordan the water overflows this strip of vegetation, driving the beasts of prey from their dens to ravage the surrounding country. Jeremiah 12:5. Ordinarily the lower terrace of the river was dry, and the people went unto the Jordan for wood. 2 Kings 6:2; also see note on Matthew 3:6. Dr. Robinson visited the Jordan on the 12th of May, and found the stream so swollen that the water reached to the very top of the banks, and in some places flowed a little over and covered the roots of the bushes. The river was then about forty yards wide, and from ten to twelve feet deep. But when the Israelites crossed the waters must have been higher, as it is distinctly said that they overflowed all the banks. The idea that the river was forded by this multitude is inadmissible. The fact that the spies swam the river, and that the Arabs of modern times pass over in the rainy season in a few places known only to themselves, can by no means disprove this striking and well-attested miracle.
All the time of harvest — The Hebrew word for harvest, according to Gesenius, here designates the grain harvest, in distinction from the fruit harvest. We are informed by Robinson that the barley harvest precedes the wheat harvest about two weeks. At Jericho, in the depressed valley of the Jordan, the barley was cut in the last half of April, and the wheat in the first half of May, about three weeks earlier than on the mountains of Hebron and Carmel. The reason for the overflow at this time instead of the winter — which, in that latitude, is the rainy season — is because the snow on the Lebanon, "which nourishes and pours out the Jordan," melts at that time with the increasing heat of the summer.
Blunt observes here some undesigned coincidences with the books of Moses, which clearly demonstrate the reality and truth of this narration. In Exodus 9:31-32, we read that the hail, which fell a few days before the first passover in Egypt, smote the flax and the barley; "for the barley was in the ear, and the flax was bolled. But the wheat and the rye were not smitten, for they were not grown up." Now the Jordan was passed on the 10th of Abib, four days before the passover, when we find the barley harvesting going on in the Jordan valley. This small circumstance, trifling though it be, confirms the truth of the account.
So minute a coincidence between two histories would not have been designed by those perpetrating literary forgeries. Again, flax is cut or pulled when in the boll, as it was in Egypt when the hail cut it down. Forty years afterwards, in about the same latitude, at the same time of the year, Rahab covers the two spies to Jericho with stalks of flax which she had spread to cure on the roof. "How very minute is this incident! Could the historian have contemplated for one moment the effect which a trifle about a flax stalk might have in corroboration of his account of the passage of the Jordan? Is it possible for the most jealous examiner of human testimony to imagine that these flax stalks were fixed upon above all things in the world for the covering of the spies, because they were known to be ripe with the barley, and the barley was known to be ripe at the passover, and the passover was known to be the season when the Israelites set foot in Canaan?"
Whedon, Daniel. "Commentary on Joshua 3:14". "Whedon's Commentary on the Bible". https://www.studylight.org/commentaries/whe/joshua-3.html. 1874-1909.
And it came to pass, when the people removed from their tents, to pass over Jordan, and the priests bearing the ark of the covenant before the people;
And it came to pass ... To understand the scene described, we must imagine the band of priests, with the ark on their shoulders, standing on the depressed edge of the river, while the mass of the people were at a mile's distance. Suddenly the whole bed of the river was dried up-a spectacle the more extraordinary that it took place in the time of harvest, corresponding to our April or May, when 'the Jordan overfloweth all its banks.' The original word [ maalee' (Hebrew #4390)] may be more properly rendered 'fills all its banks;' its channel, snow-fed from Anti-Lebanon, or Hermon, is at its greatest height-brim full: a translation which gives the only true description of the state of Jordan in harvest, as observed by modern travelers (cf. 1 Chronicles 12:15; Robinson's 'Biblical Researches,' 2: p. 262; Wilson's 'Lands of the Bible,' 2:, p. 18).
The river from Jericho is, in ordinary appearance, about 50 or 50 yards in width. But as seen in harvest, it is twice as broad; and in ancient times, when the hills on the right and left were much more drenched with rain and snow than since the forests have disappeared, the river must, from a greater accession of water, have been broader still than at harvest time in the present day. Unlike other steams which are generally bordered with meadows or cultivated fields, almost to the water's edge, Jordan has at least two banks; after descending the first of which, there appears a spacious and level plain, extending to the breadth of a furlong. It is a dry expanse of sand and gravel, over which one may walk without having the least suspicion, except from the distant ripple of the waves, that any current is near; because the inner bank, which forms the boundary of the river in its natural state, is so completely overspread with thickets of willows, reeds, tamarisks, and other wild shrubs, as keep the river entirely out of view. At the annual season of harvest the volume of water in the Jordan becomes so greatly increased that the whole even of the outermost channel is covered.
Jamieson, Robert, D.D.; Fausset, A. R.; Brown, David. "Commentary on Joshua 3:14". "Commentary Critical and Explanatory on the Whole Bible - Unabridged". https://www.studylight.org/commentaries/jfu/joshua-3.html. 1871-8.
bearing the ark
3,6; 6:6; Deuteronomy 31:26; Jeremiah 3:16; Acts 7:44,45; 1 Corinthians 1:24,25; Hebrews 9:4
Reciprocal: Deuteronomy 9:1 - to pass; Deuteronomy 9:3 - goeth over; Deuteronomy 31:9 - which bare; Joshua 8:33 - priests; Joshua 22:11 - at the passage; Joshua 24:11 - And ye; 1 Kings 8:3 - the priests took up; 2 Kings 2:8 - were; Psalm 66:6 - they; Psalm 111:6 - showed
Torrey, R. A. "Commentary on Joshua 3:14". "The Treasury of Scripture Knowledge". https://www.studylight.org/commentaries/tsk/joshua-3.html.