Chapters Transcript Treatments to Change Brain Activity in ADHD: Review of Current Status Course: Update on Attention Deficit Hyperactivity Disorder Through the Lifespan Uh, so I'm gonna talk about, uh, non-medication and generally non-psychotherapy approaches. I will talk about one psychotherapy approach, uh, at the end of the program. But, uh, here are the disclosures I have, uh, with some conflicts of interest because of royalties from, uh, the measure that we talked about, that I may discuss at the end, and the books and then the support we've received has been for research grants from NIMH and also the Institute for Educational Sciences. So, um, in terms of understanding this, I thought that this was a, be a useful thing for people to be familiar with because there are a number of different methods that are being talked about. They are, are some of them are being presented commercially that, uh, have been based upon some investigations of, uh, trying to see about changing, um, The activities and sometimes the symptoms of ADHD with methods that are thought to be going a bit directly to the brain. So we're kind of like thinking about it in that regard. And um they, we're gonna talk about the methods for changing core symptoms and sometimes associated behaviors that are available and marketed. And uh for people in practice, the patients may ask of your opinion and advice about these and about engaging in these treatments. Um, they may be perceived by people as more as safer than medication use, uh, and they may be, uh, perceived as less demanding of time and cooperation than psychotherapy. And uh I'm making the assumption that practitioners should have an awareness of these methods and their utility. There are some emerging interventions, and we wanna think about talking about them as digital therapeutics and then also techniques aimed to alter brain activity. Um, with regard to the categories that I will discuss, um, I will talk about digital therapeutics, which is treatment delivery via internet connections to digital devices, or in some cases, treatment delivery by electronic devices. That some of them will be uh uh made to alter brain activity, and we're gonna talk about the varied targeted areas, uh, and the varied stimulation methods that are being used uh to be able to bring this about. Um, and then we'll talk about an exploration of psychotherapy for altering brain activity. And I do, I'm, I'm sorry, I didn't say this in the beginning, but I should. Uh, this was, uh, effort was very much supported by a really talented, uh, uh, post-undergraduate person, uh, He Sun Chung, who helped out a lot with helping us put this, all this information together. Uh, she's been very valuable in that regard. Um, we're gonna talk about focusing on game-based interventions. We've already received a question about this, uh, and talk about device-based games. We will talk about biofeedback approaches that include near infrared spectroscopy with neurofeedback, and then we're gonna talk about emerging interventions that do alter brain activity, which is infrared therapy, that's different than the spectroscopy with feedback, uh, transcranial nerve stimulation, trigeminal nerve stimulation. And vagal nerve stimulation, and then also this investigation of um psychotherapy impact on brain activity. Now for the digital therapeutics, we're gonna talk about game-based interventions and um other uh, you know, um uh altered reality and virtual reality interventions. And in terms of these digital therapeutics, we wanna be able to define them. Uh, they are considered to be evidence-based therapeutic interventions that are driven by software to prevent, manage, or treat a medical disorder or or or disease. Uh, they include video game therapy, video reality-based parent management training, and internet-delivered post, uh, post, um, parent-child interaction therapy. So basically, it's a a digital device is involved with some aspect of the treatment. We're gonna talk about those primarily that that get involved with games as the first effort. I wanna think about them as falling into a number of different categories of this, uh, is, there's digital health, uh, there's um indication that people are using technologies and platforms to engage consumers for lifestyle, wellness and health-related purposes. Uh, this involves telehealth, it does involve clinical care administration and some management tools. And there's a, you know, when, when thinking about those, they're not really considered to be ones that need to have, uh, clinical evidence needed. There's digital medicine that's evidence-based software and or hardware products that measure or intervene in the service of human health. So that's digital diagnostics, digital biomarkers, and again, remote patient monitoring. Uh, again, there's, there is clinical evidence that's needed to understand how these are working, and then there's digital therapeutics, that is the software that delivers a therapeutic intervention. To treat the disorder or improve, improve a human function directly. And there's usually clinical evidence that's looked for and also investigation of real life outcomes. Now, in terms of the types of digital therapeutics that have been looked at with regard to uh kids and adolescents and adults in general, there's a number of them to be able to think about things. There are some cognitive behavior-based digital therapeutics. Uh, one that's been designed for adults and kids, uh, is Woebot. Uh, there's been an AI powered chatbot that provides a CBT based interventions, uh, that is, that is out there. Um, there's also pair therapeutics reset, uh, slash, uh, which is a prescription-based app for treating substance abuse disorders using cognitive behavior therapy principles. Again, I'm giving an example of these different ones that are, uh, out there, and again, these are examples. It's not comprehensive. There's mindfulness and meditation apps that have been used, one including Headspace. Uh, it's designed to reduce stress. It's mostly been targeting adults. There are biofeedback and neurofeedback methods. There's a Muse that we will talk about, which is a wearable EEG headbands that helps users improve mindfulness by providing real-time feedback. There's virtual reality and augmented reality therapy. There's Bravemind, uh, for example, in dealing also with, uh, adults, virtual-based exposure therapy tool for treating post-traumatic stress disorder military veterans. And then with regard to prescription digital therapeutics, there's one that's getting a lot of attention, uh, Endeavor RX, which is a game-based intervention that is designed for kids and adolescents. Um, we're gonna talk about that video game-based intervention. And use Endeavor RX as the one. It's designed as a video game to improve attention in children and adolescents with ADHD. It involves adaptive tasks that tend to target prefrontal and attentional networks. It has received a lot of media attention, uh, because it has been cleared by the FDA by meeting two standards. It met a standard of changing and tension, which it said it was looking to do uh in some fashion, and it also was found to be safe. Um, it targets to improve ADHD symptoms by, uh, tasks that again, deal with this attention network. Uh, there have been a couple of studies on this that, uh, have been used to be able to help, uh, I'm sorry, um, yeah, so, OK. So, uh, in, in the initial effort, it was a double-blind randomized control trial. There were a good number of kids between the ages of 8 and 12 that were involved, and they were in, um, assigned randomly to engaging in this game or a digital control, an activity that did involve some computer time. Um, the groups use the treatment at home on a tablet device for 4 weeks. Now, interestingly, the main primary measure for understanding uh if change occurred with regard to attention was the test of variables of attention. Uh, a measure that is used on the computer. It is a form of a continuous performance test that did look at, uh, finding out, uh, did the reaction time to the stimuli that flash on the screen, uh, did that change? Um, and did it change with regard to the first half of the, uh, X of, of the measure, and it also reduce reaction time variability. And so, if you are familiar with CPTs, this is a situation where um either by audio or by visual input, uh, a person is sitting in front of the screen and is told to respond whenever a letter is presented, except when a certain letter like the letter X is presented. Uh, it's done in in audio version and also visual version, and the kids with ADHD in general don't do well in this task. Their reaction times are very variable. Uh, their reaction times are sometimes sluggish or sometimes they're impulsive. Uh, in any event, what they found is that 36% of the kids who were responders to the treatment group did improve, uh, on these, on this measure, and this was used as an indication that attention did change, uh, in that regard. Uh, however, uh, we want to be able to indicate something else, and I'm just gonna highlight some of the timeline for this information about what was done with regard to this overall. And some of the other things that are being done. In any event, with regard to endeavor, um, the RCTs did not find changes in teacher rated attention issues and some limited, uh, indications of, uh, changes at home as rated by parents. So, a careful review of the Endeavor RX has found that it may not have as many functional advantages as would be seen because what has been thought about uh in a review article that looked at this carefully, uh, did say, well, they did change how kids did on a computer task, but it didn't have a whole lot of generalization to their real lives. Um, so that's been a concern. There have been some other studies that have looked at as well, that are being looking and understanding. There is Brain fit, that's been looked at cognitive training using physical activity, uh, and investigating things with regard to uh attention and uh also executive functioning. And then there's a neuro, which is a, a, a smartphone application for ADHD, um, and, uh, mental analytic support indicates that there's, when there's um When it's adjusted for personal difficulty in terms of these things, does indicate that there's better outcomes. In other words, the kids shouldn't be given something that is too easy for them to perform, uh, they need to be having it targeted for their specific area of difficulty. Um, and, uh, some, uh, publications for BrainFit were, uh, published, uh, and looked at, and basically, there's an indication that there might be some AI powered robotic agents that are designed to boost engagement, but these are all areas that are looking at as being, um, Work in progress as opposed to something that we, I think we can say is definitely being affected. One of the concerns is that have been raised is that in some of these cases, even though these are games, um, they are initially kind of complicated, uh, but there's been a lot of question about whether or not kids are going to sustain their effort and continue to be used with this. And so these are some of the variants, uh, with regard to what's been done. Uh, the BrainFit found some significant reduction in symptoms based upon the parents' uh, SNA scores and their brief scales compared to weight control. Um, and again, uh, the neuro application in a, a small pilot did find that there was changes in the ADHD rating scale and the child behavior checklist. And also the Mindro found that there was uh changes in the parents rating on the Snap, and also performance on the Tova. And again, this was an open pilot study. So some of these obviously need to be put to the test with a control group. Because, uh, for example, with regard to Endeavor RX, uh, we didn't find changes in, in, uh, rating scale outcomes. Um, the, uh, the limitations in the Tova or it's basically too similar to the game itself. Uh, and so overall, um, there may be improvements in the game, but not necessarily in real life, and, um, it's been actually also found that these reviews indicate that this is less effective than medication alone. And, um, so that's, that's an issue to kind of keep in mind. Now in terms of brain activity, there's been a number of things that have been present over time. Um, you know, there are intervention activity techniques that are designed to alter brain activity. And some of them categorize as digital therapeutics, but other involve devices are not considered to be digital therapeutics. So we wanna make sure about that. So there is treatment using infrared light. So in one situation, in one form of this, there is infrared light that is used for spectroscopy with neurofeedback, and this is considered to be a digital therapeutic. Um, and what happens here is, as demonstrated in this diagram, is that this is a process where a person, um, is involved with, um, having their brain activity monitored. Um, they're looking on a screen, uh, while this is being done, and, um, this, uh, monitor, uh, through obtaining information through infrared feed, uh, light that's going back and forth into the skull and back out. It measures changes in blood flow in cortical regions and send these signals back to the patient's, uh, device and also then shows up on the screen. Uh, through repeated sessions, uh, I, patients are ideally, uh, asked to volitionally bring and up down the regulation of the blood flow to the frontal region of their brains. Uh, this trained regulation is hypothesized to improve attention and inhibitory control. So, it's not only to reduce blood flow, but it's uh and, and increased blood flow, but it's designed to actually make it so that the person has some control over the blood flow and that indirectly this would result in them improving uh their attention capacity in other situations. Um, they are provided some instructions saying that if they do uh increase blood flow to these regions, that their attention span should go better. Uh, and so this is, this is one, in one method that's being used. We'll talk about the results a little bit later on, uh, for all these different methods. In another case, infrared light is used in transcranial photobiomodulation, so that the infrared light is actually being presented as a means of altering what's going on within the brain. Uh, and so, uh, this is being done with a transcranial photobiomodulation effort that delivers red to near infrared light to the scalp. Uh, there's a different, uh, type of light that's used, and there's a proposed mechanism is that this does result in local blood flow being increased, uh, to the prefrontal cortex region that would lead to improved attention and executive functioning. Uh, so this device is worn by the person, uh, with this, with this like kind of like helmet device that surrounds the, and the person is, uh, given this, uh, treatment for a certain period of time. Um, that, uh, is designed to be able to be done and multiple times, uh, during a week and during the time that they're getting treatment. Um, now, with regard to things in terms of the, there's been clinical work, there was a pilot test for the uh infrared, uh, neurofeedback information in 2015, and one group was trained to change brain waves using similar feedback mechanisms, but just brain waves with EEG. Uh, there was another group that got the, uh, infrared stimulus, uh, feedback. And there was another group that was trained to control shoulder muscle tension. So there were two other, there was another method that was used for looking at a brain activity, and then another group that was designed to be involved is the placebo group where they're working on also participating in biofeedback, um, but to reduce shoulder muscle tension. And these were all with kids, uh, basically, uh, 3 groups of 9 children, um, that were in between the ages of 7 and 10. Um, and what happened is that, uh, sorry, we go backwards, uh. Um, The, uh, the the, the situation was that uh there were small trials, um, and it was found that, um, a larger RCT is underway, um, and what's been found is that it's been promising but preliminary so far with regard to actually having an effect on the kids' behavior in classrooms and at home. Now, transcranial biomodulation, the one which, which the infrared light is actually going to the brain, it's not based upon biofeedback. Um, it's mostly focused on, um, autism spectrum disorders or other mixed neurodevelopmental disorders. There's been a number of small case series studies, um, and retrospective reports, um, and in these clinical studies, attention has been improved as a secondary outcome. When there have been ADHD specific pediatric scholars, there are ones that are results pending with registered clinical trials, but right now, um, there's no published uh sham-controlled pediatric RCT that provides efficacy and, and evidence for ADHD. Um, so it looks like it's an emerging promising intervention, but right now it lacks high-quality clinical evidence. But again, with, in fairness to this, uh, there are um some registered studies uh in the works. Um, and in terms of some of the summary, we can kind of, uh, look at this, uh, in terms of what can be seen here on this slide, and you can pay attention to this, but it basically is similar with more details, uh, on the, uh, information, uh, as, uh, as opposed to the prior slides. So you can turn to this at a later time, take a look at the slides. Now, um, so the status is that there's, uh, the, um, the, there's the, the one with regard to neurofeedback that's used. Um, there's some pediatric evidence, but it remains in preliminary stages, and the transcranial, uh, photobiomodulation work has sparse pediatric ADHD evidence of it is also under investigation. Again, uh, both of these, uh, are being described, uh, in commercial outlets and websites as being available. There's also trigeminal nerve stimulation. Uh, this has been, uh, has presented by, uh, neurosigma, uh, as the monarch, uh, Et transcranial or trigeminal nerve stimulation that is also approved, uh, by the FDA because it is safe and has been found to show, show some indication of benefit. Um, this is again is something that's worn on the forehead by children. It has been designed for children, um, where they wear a device on their forehead while asleep. During the time when they're asleep, this device delivers low amplitude electrical stimulation through an adhesive patch on the forehead, and you can see that uh on the, on the child uh here, um, basically. Excuse me. Um, and then it's, it's worn at night. I'm sorry about coughing. Um, it is designed to go through the skull and um. Target the trigeminal nerve. And um in preliminary work, uh, they did find through investigation. That in fact, um, with the device uh placed appropriately. That the trigeminal nerve does get uh some input uh from this device. Um, it's during the time when the kids are asleep, it's considered to be, uh, for 8 hours. It does result in a tingling sensation on the skin. Um, and the response, uh, indicates that it may be taking up to 4 weeks of this every night. It is targeted for kids between 8 and 12 years of age. The mechanism for change is not quite known. But the suggested mechanisms are that it does uh stimulate the trigeminal afference in the optothalamic zone in the forehead. And then as results, this goes in through different connections to the anterior cingulate, the insulate, and other areas, the frontal lobe. And um these are targeted because EEG studies and other FMRI studies do indicate that the frontal networks that are part of the, uh, these areas of the, uh, including the trigeminal nerve, that they are part of uh implications for ADHD. And it's believed that this may provide a biologically plausible route for symptom change, uh, so that if this is done enough, that the brains, uh, and the trigeminal nerves and the other connections that are made, uh, in this network, uh, will improve and result in better ability for these areas to be able to monitor and manage attention control. There's been some clinical work, uh, original work by McGaw from, uh, UCLA and then also O'Neill with regard to some, uh, uh, ongoing studies with the evidence indicating that, um, During this treatment, um, when it's done compared to a sham TNS nightly for 4 weeks plus 1 week of discontinuation, there were 62 kids. They did, um, they were medication-free kids with ADHD. Uh, they looked at the ADHD rating scale, and they also looked at CGI improvement, uh, executive function as measured by the brief. That's uh. They did look at sleep. They looked at the children's sleep history questionnaire. They also looked at anxiety, and they did look at also EEG uh results. And the result was that the kids did improve. Um, on the, uh, ADHD rating scale, uh, with a, a significant change, uh, going down. Although interestingly, the placebo group did go down as well, but again, it did result in a medium effect in size. Um, there was an indication that the rebound, the symptoms rebounded significantly. But the group differences still, still did persist, even though they did rebound a little bit. There was a CGI improvement um uh with the group, uh, but no difference in parent ratings of the Connor's, the brief, the sleep, or anxiety. And interestingly, um, there were indications of spectral power in right frontal and uh uh frontal midline regions with the group that had this active work. Uh, and the ideas, uh, were found that the changes in the spectral power of the data, theta, beta, and gamma, uh, waves, uh, were related to increases, um, I'm sorry, related to decreases in hyperactive impulsive symptoms. So there was a, a negative correlation that as the improvements in the connections in these brain wave powers, uh, went up, uh, the, uh, hyperactive impulsive symptoms went down. Again, uh, they didn't find change in the attention issues except on the ADHD rating scale. Um, so, The ongoing study, uh, is one that's being done, um, and, um, they're looking at kids with, in particular with prenatal alcohol exposure who might be prone to, um, uh, you know, um, prone to a fetal alcohol syndrome that may be hyperactive. It's a two-year study. And um it's being investigated currently. Um, with regard to other nerve stimulation techniques, they're available, they're present. There's transcranial pulse stimulation. Um, this is non-invasive neuromodulation, um, using focused ultrasound pulses. Um, it's not believed to induce neuronal firing, but it's, it's believed to involve a mechanical transduction method. So kind of like mechanical stimulation from the ultrasound impulses are believed to be converted into biochemical signals that can influence neuronal activity. So this is the sound wave having an impact on how the, the nerve cells are responding. There is transcutaneous auricular vagus nerve stimulation, uh, that is targeting norepinephrine pathways. And it's believed that the uh uh the vagus nerve stimulation uh goes to a number of different areas of the brain and that it results in some norepinephrine release in this path. It's spelled out here. It's also believed that this may indirectly modulate the amygdala, uh, and the autonomic nervous system. It's been used in a lot of different ways, but in the case of kids with ADHD and other conditions that are psychiatric, it's thought to possibly reduce emotional dysregulation. And basically what we have here is a summary of this work, uh, where we basically find that, uh, tri, uh, um, trans uh cranial uh photobiomodulation. There's indication that there is a positive result so far in some studies that transcranial nerve, uh, stimulation, uh, results in some positive indications so far. Uh, the transcranial, uh, uh, post stimulation using the ultrasound, it's a little unclear at this point in time. And the uh the vagus nerve stimulation is found to be unclear as well at this time. There's some indications that may be useful with some kids, but if the studies are really um not well designed right now. So, here's again the summary table for transcranial trigeminal nerve stimulation. And uh again, this is a highlighted overall as well as then some of the other ones that we talked about before. So this is a, a summary with a little bit more information and a little bit more detail. Now, um, all in all, we have promising clinical results but still needs to get the, um, efforts. There's a small number of trials. Uh, they need to be larger, longer, and better powered. Um, the pediatrics evidences for most effective for kids between 8 and 12. And so that uh there may be some pharmacotherapy alternatives for children, uh, the comparison is indirect and limited by short-term and small studies. So again, right now, these are promising but not yet broadly proven for replacement for established treatments. Now, another thing that we wanna be able to talk about is work that we've been involved with uh that has looked at altering brain activity with an efficacious psychotherapy. The efficacious psychotherapy is a, a therapy that's uh organizational skills training that we found to be effective with kids with ADHD and then in subsequent studies, we've also found another RCT that it is effective with kids. That uh do not necessarily meet the criteria for ADHD but do have low levels of organization, time management, and planning. And um overall, this is the components of organizational skills training. It is a, a psychosocial treatment that involves parents, kids, and also is uh involving with teachers. Our recent work has found that it can be delivered fully through virtual treatment, uh, as well as the original studies that looked at being done in person. It's a treatment that involves about 20 to 25 sessions of work with the kids. Um, it is delivered twice a week to be able to make sure the kids are following through and using the skills that we teach. We do get involved with providing the parents and the teachers and the kids and orientation to talk to them about that uh persons with organization, time management, planning problems, um, have these difficulties because of uh possible inactivity of what we described as um sometimes lapses in activity of the mastermind. We talk a great deal about the idea that the mastermind is a personification of the executive functions, and the mastermind is helpful with having us do all the things that we need to do. The mastermind monitors our behavior, plans our behavior, helps us figure out the timing of our behavior, and helps us also kind of control distractions. But the mastermind can often be uh tripped up. By glitches that we say are these little uh annoying creatures inside the brain. We do this with drawings and discussions, and we say that everybody is affected by these glitches because they sometimes fool everybody, and they really like to fool kids and they like to get kids into trouble. We talk about the go-ahead, forget it glitch that tells kids, oh, you might not need to write that down when they're told about assignments at school, you'll remember it later on. But um when the kids don't know exactly what they're supposed to do for homework, they get scolded about that, they get stressed about it, uh, this glitch is over like in the corner saying, aha, I tricked you again. So we want the kids to say, we're gonna work on building up your mastermind and using skills uh to get better at dealing with these day to day routines. Uh, we have the go-ahead, lose it glitch, we have the time bandit, and we have the, um, also the go-ahead, don't plan it glitch. Um, and we work with training parents in behavior modification strategies for rewarding the kids for using the skills. We have teachers to get involved with prompting the kids for using the skills. And what we do is we work on breaking things down for dealing with schoolwork, which is what parents told us is the most important part, uh, for these kids that are having these troubles. And we work on having the kids learn to track assignments and come up with a specific tool and routine uh for writing down their assignments or for making sure they know exactly where they need to find uh digital assignments and the details. And also learn how to be able to use a calendar. So it's practical strategies, very similar to what Mary Solanto's program did with adults uh a while ago, but basically saying, uh, you can't do well with your homework, you get stressed with you and your parents get really upset. You can't do it if you don't know exactly what the details are, and you can't do it well if you don't know when it's due. So we want them to learn these procedures. We then move on to say, OK, now that you know what you're supposed to do, the next problem is you have to have the new materials. You have to have everything, uh, getting transferred from school to home and back and forth and getting from your desk to the teacher's desk, even if it's electronic. So you have to know about managing your files, managing your papers, you have to come up with routines and and uh for that. You also very common problem, you have to know about organizing your backpack and have to have checklists because if you, um. Come home without your math workbook, you're in trouble, you can't do your work. But we've also run into situations with working with in these different studies, both RCTs and controlled studies, as well as clinical work. We've worked with over about over 100, 300 kids at this point in time with these issues. We've heard of kids losing three winter coats, um, you know, losing iPads, losing phones, things that are quite valuable because they failed to put them into their backpacks when they left school. Um, we asked them to work on managing their desks and making them good work areas, and then we have them also learn to get rid of all the extra stuff that they might not need. We then move on to this through these uh procedures and these sessions to have them learn about managing time, to know how long it takes to do things, and to not end up thinking, uh, everything takes 5 minutes, or on the other end of cognitive distortions that um things will take forever, and so I'm going to avoid it because and procrastinate because it's gonna be unbearably difficult. Um, we want them to get to know exactly how long it takes to do a number of different things. And we want them to also learn and be aware of their exact schedule, uh, during their week so they can plan accordingly, to know not to have to study, um, for a test, um, and leave it to the day when they have basketball, because on basketball nights, they can hardly get their homework done, and they're certainly not gonna be able to get ready for studying for a test. And then finally we have them learn to pull it all together by coming up with a plan to know exactly how to break down tasks into the big steps, to then know what materials to get for each step, and then to also get involved with the process of of figuring out how long each step should take and when they can fit it into their schedule. And in doing all this work, We found that it's been a been a program that results in the kids improving from their parents' perspective in organizational skills, improving from their teacher's perspective and organizational skills, in improving their academic performance and their productivity as rated by teachers, and also in improving and having fewer conflicts at home because they have fewer homework problems. Uh, importantly, with regard to the one study, the original study, we also did find that this, um, benefit lasted into the next school year. So, it does look like the skills approach is quite effective. Um, we had the opportunity to wonder and think about with, uh, Javier Castellanos to sing and wonder, um, does this change brain activity? Um, and so that we've done some pilot studies as well as an RCT where we did functional resting state FMRI's before and after treatment with uh a treatment group and a weightless control group. And uh that results, we did find in terms of these kids, in terms of behavior reports for the 51 kids for whom we got this uh full study completed, which happened to get disrupted by COVID and uh resulted in a, you know, uh like a limit in our result, our size. But we found that the parents reported improvements in organization, time management planning with an effect size of 1.72, a very big difference. The teachers found a medium effect size, um, not as big, and there were only 19 teachers or 19 kids we had teachers with because Because of COVID, the, the regional schools in our area, especially in New York City public schools, said the teachers can't participate, they can't give us rating scales. Um, and they can't be involved with talking because the teachers are just too overwhelmed. But interestingly, even the kids themselves, uh, indicated that they thought that they improved quite a bit. So we found a lot of behavior change results. With regard to FMRI results, uh, it was looked at, um, in three ways. The first initial way was what was designed for the study, uh, using a method that has been from, um, a relatively old way of interpreting uh fMRI data and analyzing them. And in that, uh, that method, it was found that there was an increase in functional connectivity between the dorsal and ting cingulate cortex and the uh ventral striatum uh uh default mode network in the immediate treatment group, with no change in the weightless control group. However, when two more other methods for interpreting fMRI data were used, uh, it found that there was no difference between groups in the connectivity between the dorsal and singular cortex and preset targets. We will be investigating a little bit further these data to know if kids have made huge improvements might have changed their functional, uh, resting state activity, but, uh, right now, we, uh, do not have it well established that these kinds of changes did occur. Um, and, um, this is, we thought this was an interesting study. It's one of the few studies that actually has looked at psychotherapy and with kids and its impact on, um, resting state, uh, functional connectivity and brain activity. So I'll stop there and be able to take some questions, uh, and, uh, be happy to turn it over to that, uh, that process, and thank you for your time. Published December 6, 2025 Created by
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