Efforts are being made to reform and reconceptualise children and young people's (CYP) mental health services. This is in response to a rapid increase in mental health difficulties in this population, and the shortcomings of current service provision. The present study seeks to comprehensively evaluate the local implementation of the THRIVE Framework for System Change in Greater Manchester, UK (GM i-THRIVE) from 2018 to 2021. The framework was designed to change the way mental health is perceived, and subsequently how support is allocated. The current study focusses on the implementation of the framework's principles into CYP mental health support in the region.The study comprised three methodological components, beginning with examination of the GM i-THRIVE implementation plan and self-assessment questionnaire measure using the Quality Implementation Tool. This was to provide a wider backdrop of implementation method adequacy to the rest of the study's findings. Subsequently, evaluation measures completed by professionals across Greater Manchester were examined to establish implementation progress, before corroborating key items from this measure with thematically analysed interview data from six CYP (13–22 years) who recently received mental health support in the region. Levels of agreement between staff and CYP were examined.Qualities of the service: information and decision sharing; communication and continuity; needs-based support; compassion and trust, and (2) The mental health journey: beginnings; endings; waiting; satisfaction with support. A good level of agreement between CYP testimony and staff progress reports was found.GM i-THRIVE's implementation plan and self-assessment measure were respectively deemed a strong guiding foundation, and a suitable way of evaluating implementation progress. Every principle within the self-assessment measure demonstrated closer alignment with the THRIVE Framework as time progressed. Two themes were developed from the qualitative interview data, each overarching four subthemes: (1) Findings suggested that the experiences of the CYP in the sample, who were interviewed in the spring to summer period of 2022, were overwhelmingly positive. The rich insights into mental health support offered by the young participants lead us to recommend continued qualitative research with service-users as GM i-THRIVE's embedding period continues, with focus on representing a wide range of experiences in future research samples. Methodological limitations were explored, including the extent to which true cross-references could be made between professional and CYP accounts. The peaTo fully understand what the implementation of THRIVE, a national reconceptualisation of CYP mental health and service provision in England, hopes to achieve, we must first explore the various ways that previous provision of child and adolescent mental health services [known by the acronym of CAMHS when this refers to services provided by the National Health Service (NHS) in the UK] fell short of providing adequate support. The key inadequacy was that appropriate specialist support was often tremendously difficult for CYP to access. For example, in 2018, only 25% of CYP with a diagnosable condition managed to utilise specialist CAMHS services in England . Reduced1.2.does not, belong solely to medicalised services that are provided by the NHS. Allied professionals, of which teachers are a prime example, are essentially a “front line” source of mental health support for CYP  have gradually aligned their CYP mental health services to the THRIVE Framework. This alignment process, known locally as GM i-THRIVE, is just one element of devolved health and social care resulting from a 2016 deal between the Greater Manchester Health and Social Care Partnership (GMHSCP) and the UK government. GMHSCP can now decide how services are funded at a local level, meaning that spending can be allocated appropriately to the 2.8 million residents of Greater Manchester. An initial implementation period of four years (2018–22) was given to introduce, implement, and normalise the Framework within all sectors that provide mental health support for CYP. It is therefore crucial that this formal implementation phase provides the strongest possible foundation for the ongoing success of the programme. To do this, a careful, iterative process of planning, implementing, and monitoring  was ending, and a short “embedding” phase, in which implementation efforts are continuing, was beginning. This meant that sufficient information, data, and informed testimonies were available with which to conduct a comprehensive evaluation. The components of the present study and their objectives will now be outlined in turn.). Second, we established whether the aims of GM i-THRIVE were met, by analysing ratings of progress, self-reported by professionals working across Greater Manchester. Finally, interviews were conducted with CYP who were recently in receipt of support from THRIVE-aligned mental health services in Greater Manchester. This service-user data was compared to the implementation progress reported by the localities. Whilst localities might report a certain level of implementation progress, if CYP in Greater Manchester do not describe experiences that evidence THRIVE-aligned care, such reports would mean very little. Young people's hopes and expectations of the outcomes of mental health care often considerably differ from those of the adults involved in their support. Research has revealed that parents and their children have conflicting ideas of what ideal CAMHS provision would look like  . The plaSupplementary Materialsook like . Differeook like , 23. Thi2.2.1.The production of this article adhered to the Standards for Reporting Qualitative Research (SRQR) . In addi2.2.The authors were externally commissioned by GMHSCP to evaluate GM i-THRIVE. As employees of the University of Manchester rather than GMHSCP, the analyses and conclusions drawn in this study were unlikely to be biased by vested interest. However, the first author has been continually immersed in the working environment of GM i-THRIVE as part of this work . As a result, impressions gained during these meetings may have influenced the analysis of the present study's qualitative data . The kno2.3.The implementation site of Greater Manchester, which was home to 898,000 under-25s in 2019 , is an e2.4.The present study was a mixed-methods case study of GM i-THRIVE. It combined qualitative and quantitative document analyses with semi-structured qualitative interviews. This triangulation enabled the generation of comprehensive meta-inferences, pertaining not only to implementation progress, but also to how successfully it was planned and measured. Acknowledging one's reasons for adopting a mixed methodological approach is an important part of the rationale behind any evaluation design . One of We deduced that the most appropriate way to approach the evaluation of GM i-THRIVE was through a pragmatic epistemological lens. The assortment of methods used in the present study were chosen purely for their ability to meet each research aim. The pragmatic notion that knowledge of the inner workings of organisations can be generated through the conflation of participant accounts with the empirically measurable  meshes e2.5.Eligibility for the qualitative element of the study required participants to have received mental health or wellbeing support since September 2018: the start of GM i-THRIVE's implementation period. This support must have come from a site or service within Greater Manchester that was active in the process of aligning their practices to the THRIVE Framework. Participants needed to be aged 13 or over, and to have been in receipt of support from a CYP mental health service at any time from 2018 onwards, regardless of when their support began. We did not set a strict upper age limit, given that some local services focus only on those under 18, whereas some stretch to 21 years old. 13 was deemed a suitable lower cut-off age at which participants could properly assent to and engage with the research. Participants were identified on the basis that they were either former users of a service, or they were in the final stages of receiving support. These criteria ensured that the mental health of participants was sufficiently stable to both assent and take part. A gatekeeper within the GM i-THRIVE implementing team identified participants through their support providers on an opportunistic basis. They were approached based on the providers' perception of them as able and willing to participate in an interview, with a third party, about their experiences with support. Participants were given the option of having another person present to provide emotional support.2.6.Ethical approval was received (reference number: 2021-11033-18945) from the University of Manchester's research ethics committee (UREC). All participants (and their parents if under 16) were provided with age-appropriate participant information sheets, detailing the nature of the study and their potential contribution. Written consent was obtained from participants who were over 16 , and from the parents of the 13- to 15-year-olds. 13- to 15-year-olds gave written assent to take part, confirming that they understood the study and how their data would be used. Through a process of reinstating information and rights, and being attuned to our participants' responses and body language, consent, or dissent, was obtained continuously and reflexively as per a recent reframing of research consent .2.7.2.7.1.GM i-THRIVE provided a copy of their implementation plan, which comprised five overarching stages: set-up; engagement, understanding, and planning; building capacity; implementation; and embedding and sustaining. Each stage contained several granular items that were to be completed during the implementation process. A copy of this implementation plan can be found in the 2.7.2.Due to social distancing restrictions enforced in response to the COVID-19 pandemic, interviews were conducted by the first author using secure online video conferencing software. Semi-structured interviews were used to explore participants' experiences of receiving recent support for their mental health. The interview schedule was designed to ascertain the extent to which the aims of THRIVE were reflected in the participants' experiences of support or care. The schedule consisted of 10 broad questions, overarching several prompts and sub-questions see .2.8.2.8.1.For the first step of the document analysis, GM i-THRIVE's implementation plan and the blank self-assessment matrix were checked, together, for the presence of each of the 28 action steps of the QIT  see Tab. The QIT2.8.2.via the video conferencing software, and the automatically generated transcripts were checked manually for accuracy by the first author. Data were analysed following Braun & Clarke's guidelines for reflexive thematic analysis  and ages can be found in Two themes were developed through reflexive thematic analysis, each of which overarched four subthemes see . These a3.1.This theme included descriptions of what participants felt that the service offered (or failed to offer) them.3.1.1.Some participants said they were allowed an active role in their support experience. This was viewed positively by many. Participant 1 reported that they could see their psychologist as regularly as they chose. The psychologist had passed this decision on to the young person, and appointments could be made as needed through a process of flexible and open contact.“He wouldn't say like, “oh, I’ll see you in two weeks, or I'll see you in a week” he'd say, “whenever you need to see me, you know the process”. Sometimes I'd go months without seeing him, and it'd be fine. But other times, I'd call up and say, “can I see you here at this time?” So yeah, I felt as though I was in control”. [Participant 1]Conversely, a lack of transparency and clarity was reported in some instances. An older participant felt that their age should have been considered when information about their course of therapy was provided. They felt that knowing more about their treatment would have allowed them to positively integrate this information into their journey. As such, their uncertainty meant that they needed to place a good deal of trust in the staff providing support.“I was a full-grown adult. So, I could have handled being told “you're receiving this type of therapy, because we think this will be beneficial to you” […] I think because I was in such a low place, I just willingly let myself walk into this building. And I had no idea what I could have been walking into”. [Participant 6]The following participant would have appreciated more information about the nature of their own mental health. Receiving a diagnosis was an important tool for helping them to understand their difficulties. It may also have helped them to feel valid in their help seeking: they felt that they were one of the only young people in their setting without a formal diagnosis.“I feel like they need to acknowledge that some people want a diagnosis. A lot of the time, people will go there, but they'll have a diagnosis. […] the nurse asked me why I was there, and I just I couldn't say anything, because no-one had told me that I had anything wrong”. [Participant 4]Despite the importance of transparency, other testimonies suggested that shared decision-making should be managed carefully. Professional insight should be appropriately applied to guide the process. Participant 5 felt that too much initiative was expected of them. They would have appreciated more help with identifying the most beneficial focus of their sessions.“It was put down to me to decide the focus of what we'd be talking about. But I think at the time, I didn't really know what I wanted to be talking about. Even though it was my choice, I think I chose the wrong thing […] I think I would have preferred to be told what to do a bit more and told what to focus on”. [Participant 5]Participant 6 actively hoped that decisions would be made on their behalf. They saw the commencement of professional help as an opportunity to pass on the onus of their difficulties. It should not, therefore, be assumed that high autonomy is universally valued. A considered balance should be drawn for each young person.“I think when I got to the point of needing therapy, it was like I was relinquishing my control, and I wanted someone else to do the work”. [Participant 6]Corresponding self-assessment matrix principle(s): Micro 1A, Micro 5BLevel of agreement between staff and CYP testimony: High3.1.2.Several participants' schools acted as a gateway to receiving mental health support. When support was not provided directly by their school, teachers were able to refer them to appropriate sources of support. This suggests that school staff have sufficient knowledge of a range of mental health services, and successful lines of communication exist between schools and these services. These qualities build a more seamless support acquisition process.“It came to me after speaking to multiple pastoral teachers. I have [mental health concern], and they said that they could help me by introducing me to people to talk to: mental health services”. [Participant 2]Participants who encountered multiple professionals and services across their mental health support experience said each new professional was equipped with at least a basic knowledge of them and of their mental health story. Participant 1 felt that when professionals asked them to elaborate on elements of their background, this was treated as part of the therapeutic process. This suggests an element of communication between providers, where gaps in professionals' knowledge are filled tactfully. This provides a smoother continuous care experience, that removes the strain of restating details about themselves to each person that they meet.“It’s always hard between telling, “are they asking me about me because they want to know my perspective on my life?” Or “they're asking me because they genuinely don't know?” But I think they had a general background of my life. And if they were asking me, it felt as though they were asking me for my perspective”. [Participant 1]The same participant spoke about becoming too old for NHS CAMHS support. Although they were successfully referred to an alternative source of support, they felt that the shift between NHS-based support, and this, was abrupt and difficult to navigate. A smoother post-18 transition would have improved the continuity of their care.“I wasn't perceived as high enough of a threat to be moved on to the NHS adult services. But my support worker at CAMHS referred me to a lower threshold thing […] which is really good […] I just think sort of a step-down service that could be used for anybody who had touch with CAMHS”. [Participant 1]Corresponding self-assessment matrix principle(s): Macro 2, Macro 5Level of agreement between staff and CYP testimony: Moderate3.1.3.Several participants felt that they were taken seriously, and that they were listened to. This allowed their support to be tailored appropriately to their individual needs and preferences.“Everything she said to me, everything I said to her, she took very seriously. And I really appreciated that she did that”. [Participant 3]This participant reported that their predicted duration of care was extended based upon their continued requirements. After their initial period of support ended, they were easily able to recommence at their own request, as their needs changed. The participant's decision to reengage with the support appears to have been aided by their previous positive experience, and the approachability of the staff they met.“I was supposed to [have support] for 6 weeks, but I think I had 8 or 9. Then a few months later, I asked to go back. There was nothing wrong with the treatment that I previously received. But the people there that I had; she was really nice. I asked to go back, so I did”. [Participant 4]Some participants, however, reported that their needs were not taken seriously enough. Participant 2 said that when they were younger, a member of their school pastoral team frequently raised irrelevant topics. This meant that they did not receive help with the issue with which they had originally been referred. Although it is unclear whether the pastoral worker lacked expertise in the appropriate area, or whether this experience represents a true example of poor listening, the resulting lack of needs-based support clearly impacted the participants’ desire to continue with the sessions.“I started seeing a school nurse, and the sessions were supposed to be about [mental health concern]. I explained to her, but she started talking to me about [an unrelated concern]. Every time I tried to draw away from the topic, she just kept on steering it back to that. It didn't last long after that, I just stopped seeing her”. [Participant 2]Corresponding self-assessment matrix principle(s): Meso 3BLevel of agreement between staff and CYP testimony: High3.1.4.This subtheme covers the personal qualities of support or care providers of mental health support that were memorable to the participants. Several participants described the professionals as kind people, who genuinely appeared to care about their wellbeing. The following participant describes that perceiving these qualities allowed a quicker development of trust.“It took a while to build up the trust to be able to speak to her […] and it only took a few weeks, because she came across as a very nice, genuine person to me”. [Participant 3]Trust is mentioned again in the following extract, where Participant 6's provider made them feel that nothing that they discussed would be passed on outside of the session. The participant detected clear signs that their provider had listened to them in previous sessions, which added a personalised element to the support they provided. This further developed the trust they felt. This professional was just one member of staff operating in a wider compassionate environment, that the participant sensed as soon as they entered the building for the first time.“I felt very much like all the things I was telling her were 100% confidential […] I felt very safe with her as my therapist. The way she would remember little details and always think of other ways I could have improved […] So, I think the actual genuine support that they gave young people, I could see that throughout the building”. [Participant 6]Participant 5 was impressed with the stoic attitude of their provider. The fact that they did not appear shocked or upset by the information that they disclosed contributed to a calmer and safer environment, where no topic was taboo.“She always had a friendly face on, even when I was telling her some really not nice stuff. She's very good at dealing with it in a way that I definitely couldn't if someone was telling me those kinds of things”. [Participant 5]3.2.This theme covered participant experiences that related to the different stages of their personal mental health stories, and how these were accommodated by the services that they got support from.3.2.1.Several participants mentioned struggling with their mental health for a long time before they received support. Many referred to a specific moment, almost a “tipping point”, where they, a family member, or a teacher, realised that professional support was needed. They suggest that their mental health difficulties had built over time, developing from lower-level concerns that were not necessarily noticed by those close to them, to more severe challenges that greatly interfered with their functioning. Following feelings of depression from a young age, participant 4 spoke of one evening where they experienced a mental health crisis, and the emergency services were contacted.“I ended up becoming really depressed dead young […] I ended up calling 999. Because I just, I felt really bad one night […] I ended up having to go to hospital because I was a child”. [Participant 4]The participants talked about the various avenues through which their first contact with mental health support was accessed. Many were either referred to external support by their school, or received early support directly from their school. The next testimony describes the value of knowing that help is available. Even though participant 1 was not ready to engage with support when they were first approached, the process of opening dialogue by informing them of who they could turn to seemed important to them. Participant 1 was able to internally process the idea of receiving support, and they eventually approached the teacher on their own terms.“Whoever is on call at the time to deal with issues like this was like, “what's going on?”. I didn't speak to them. I was like, “none of your business”. A few weeks later, I approached this teacher and we sat down. We had a chat for about two hours, and I just cried and cried and cried”. [Participant 1]Participants valued building familiarity before their support formally began. This level of comfort made them feel more relaxed, and that any anxieties were at least partially ameliorated. This early breaking down of barriers between client and professional is likely to have enhanced the benefits of the support.“I was a lot more comfortable talking to her, and she knew some stuff about me as well. So, it was a lot more comfortable between both of us”. [Participant 2]For Participant 3, these early conversations were used to establish the nature of their needs, so that appropriate support could be given. Following this discussion, regular sessions were set up.“Before we started our sessions, I did meet with her. And she did ask me some questions just to get to know about my home life, my school life […] And then from there, she got a plan, because then she started saying that we'll meet up in these days”. [Participant 3]3.2.2.When participants spoke about their support coming to an end, their level of preparedness was discussed frequently. The ending of support is a stressful time for many young people, and participant 3 stated that the topic was raised regularly in their sessions. This allowed them to imagine a time when the professional was not accessible, and to develop approaches to manage their concerns alone in the future.“She prepared me quite well. When she explained something to me, she would give me advice on how to remember things, and she'd say “don't forget that one day, I won't be here for you to come and speak to. So, you're gonna have to be able to cope on your own and have good strategies to deal with your mental health"”. [Participant 3]For some, the timing of their ending was less clear. Although the participant below appreciated that their professional decided over time how long their support would need to last, and that there were advantages as well as disadvantages to not knowing, they feel that their ending felt abrupt. Knowing earlier would have given them time to process the next stage of their support.“I just was randomly told one session, like, “Okay, this is your last of four sessions” or whatever. It was very surprising to me. If I'd known, I would have maybe seen it differently […] But I also just think that maybe making it more clear to me how I could have carried on receiving support if I needed to”. [Participant 6]Whilst many participants felt ready for their support to conclude when it did, some felt anxious and unsure. Participant 5 said that the topic of continuing need was not discussed thoroughly enough. They were left questioning whether they had made the most of their time, and the lack of conversation around this rendered them unsure of what further support they needed, or how to ask for it.“She told me that I can re-refer, and it'll probably be quicker than if I were to start again somewhere else […] But I do remember feeling very anxious about it ending like, “oh no, I don’t know if I've gotten everything out of this that I could have” […] the last session could have just been a bit longer, because I find it really difficult on the spot to know what I need […] it was just like, “okay, bye"”. [Participant 5]Corresponding self-assessment matrix principle(s): Micro 3A, Micro 3C, Micro 5ALevel of agreement between staff and CYP testimony: High3.2.3.Several participants reported that whilst setting up regular support was not instantaneous after their initial referral, it was shorter than what they were told to expect. This suggests that professionals may give their clients larger timeframes to manage their expectations and avoid disappointment. The following participant waited a small proportion of the maximum duration that they were initially quoted. During this time, they were able to meet the professional to build familiarity before the official start.“It was actually pretty fast. When the pastoral teacher first put me down for it, she said there might be a long wait, like six to 12 weeks. Then I actually met [professional's name] before the sessions started. And then it was like three weeks after that. That's when I started seeing her”. [Participant 2]Participant 6 believed that their wait, to use a non-NHS service, negatively impacted their mental health. This may be a likely scenario for many, given that a high level of distress is often felt before support is initiated (see subtheme “beginnings”). Participant 6 spoke of the wide-spread issue of waiting times for mental health support, and how this has perhaps skewed perceptions of what an acceptable waiting time looks like.“It definitely was detrimental for me to have to wait three months. But in comparison, I know the NHS waiting list is insane […] But the three months, I think the fact that it was the minimum that she told me actually was really good. And I saw that as like, wow, amazing, that's so quick like, which is kind of messed up, I guess, that we think of three months as being quick”. [Participant 6]Another consequence of lengthy waits is that mental health concerns are not dealt with when they are the most salient. Participant 5 said that by the time their sessions began, although they still made use of the support, they had already come to terms with the difficulty they initially sought help for. During this time, in a worst-case scenario, where need is not professionally met, unhealthy coping strategies may be developed. These may be difficult to overcome if related difficulties re-emerge over time.“I signed up, and then it had been so long that I’d moved on from what I originally wanted to talk about. So, once I got there, I was like, maybe I'll use it because I am still struggling in other ways, but it definitely wasn't what I originally signed up to do it for”. [Participant 5]3.2.4.All participants stated that overall, they would recommend the type of support that they got to another young person. Participant 5 suggested that the broadness of their support means that they would suggest it to most people. They appeared to find the process insightful and enlightening, in that it helped them to identify the root causes of their difficulties.“The stuff that I was taught is very broadly applicable. The psychoeducation aspect of it, like “oh, this is where those symptoms are coming from” was really, really helpful. So yeah, I think that anyone… I say it all the time to my siblings, “go and get some cognitive behavioural therapy”. Can't recommend it enough”. [Participant 5]Some participants, although stating that their experiences were positive overall, would only recommend their support under certain circumstances. These participants discussed the nuances of their own support-seeking journeys, and said, therefore, that they could only truly endorse it to somebody who's circumstances were near-identical to their own. The following participant felt lucky to have received such good support, and they perceived their experience as the exception rather than the norm in terms of how smooth it was.“I felt so fortunate the entire time […] But that's just my experience. It's not what most people would say. I'd only be recommending the type I got, because I probably know, like six or seven people who've had a really, really bad experience with CAMHS. And it's a shame because I wouldn't want to recommend someone for them not to be getting good treatment”. [Participant 1]4.This study explored the implementation of reformed CYP mental health service provision within the context of a recently devolved healthcare system. This broad aim was investigated through a variety of methodological lenses, to establish not only the improvements that have been made, but also the adequacy of the tools used to monitor this progress. Evaluating the plan that was set prior to the implementation of GM i-THRIVE, then cross-referencing professional and service user accounts of adherence to the THRIVE Framework's core principles, provided unique triangulated insights into an intervention across the entirety of its implementation timeline.The interview data were split into two overarching themes see . The firProfessional agreement with points raised in the subtheme “communication and continuity” was considered moderate. The self-assessment principles relating to multi-agency involvement, and integrated care, were consistently rated highly, and CYP generally reported a well-connected experience. However, the difficulties with the transition between child and adult mental health services were raised.., This is, unfortunately, a common source of distress, especially as these changes in care coincide with a number of other life transitions in late adolescence , 41. DisIn the next subtheme “needs-based support”, CYP responses were mixed in terms of whether they felt that their requirements were noticed and actioned.. These experiences matched closely with professionals' scoring of meso principle 3B which relates to needs-based care: a principle that was rated moderately, but with a steady improvement year on year. Feeling listened to is one of the most valued aspects of support for CYP, with professional understanding key to having mental health needs met . The finThe second theme, “the mental health journey”, also comprised four subthemes. In “beginnings”, participants valued building familiarity to foster trust prior to an official start—a process which should not be rushed . This suThe subtheme “endings” saw some participants feeling well-prepared for their support coming to an end, whereas for others, the ending felt abrupt. Agreement with staff reports was good.Although staff recognised endings important parts of the therapeutic journey, and that discussions of timeframes were often had, they felt that the limitations of help were not always made clear to CYP. The honest setting of expectations and defining of outcomes at the outset of support is vital . Itis thIn the subtheme of “waiting”, participants felt that their expectations were managed well, but only within the wider context of the normalisation of long waits. A detrimental impact of long waits on mental health was reported. Other qualitative studies have reported similar negative consequences of long waits. This is a well-documented issue within CAMHS as well as the wider NHS , 11, wit4.1.The key strength of the present study is the mixed-methods approach, which sought to seek consensus across a range of sources, from multiple informants. Greene et al.  stated tHowever, despite this methodologically strong approach, our findings must be considered within the context of their limitations. First, the overwhelmingly inductive qualitative approach led to an imperfect cross-over between the subthemes and the principles of the matrix presented in An inductive approach was especially important given the study's small sample of CYP, a result of the challenging nature of recruitment, to ensure that the interviews were themed as suitably as possible. Similar studies undertaken in the health research field , or withThe reporting of predominantly positive views may also explain the agreement between CYP and professionals on THRIVE alignment, especially given that other studies comparing accounts from both have not found such close consensus . As all The final limitation that we wish to raise is that although the data within this study covered the entire four-year initial implementation period, it should still be treated as a cross-sectional account. Within GM i-THRIVE, evaluative work should continue, including further conversations with CYP. This is because implementation should not be assumed a linear process. Numerous influencing factors, both wider and organisational, continuously influence progress and sustainability . Additio4.2.Here, we summarise the meta-inferences made by combining the lines of enquiry in this mixed-methods study. GM i-THRIVE's initial plan set a solid foundation for the implementation work that was to follow between 2018 and 2021, and the embedding period that will follow this. Similarly, the self-assessment matrix was a suitable tool with which to assess alignment of services to the THRIVE Framework. Under this context of good quality planning and measurement, progress was made towards aligning services to the THRIVE Framework. Although limitations were identified, professional staff working within these services, and the CYP receiving support and care, tended to agree on what mental health provision looked like during the reform period. Given the rich insights offered by the study's participants, we recommend continued discourse with service-users with a range of support experiences as the intervention continues to be embedded.The triangulation of methods in the present study aimed to deliver a practical and original insight into how implementation science feeds down to those in receipt of an intervention. The comparison between the unique experiences of CYP, and the opinions of progress expressed by those implementing the programme, provides valuable understanding of whether implementation and evaluation tools, in isolation, can produce accurate and valid representations that are reflected in the experiences of those in receipt of care. The study produces helpful findings that can be used to guide the future of GM i-THRIVE, in addition to providing a valuable and unique contribution to mixed-methods research, particularly that which pertains to implementation evaluation.


As improved recording technologies have created new opportunities for neurophysiological investigation, emphasis has shifted from individual neurons to multiple populations that form circuits, and it has become important to provide evidence of cross-population coordinated activity. We review various methods for doing so, placing them in six major categories while avoiding technical descriptions and instead focusing on high-level motivations and concerns. Our aim is to indicate what the methods can achieve and the circumstances under which they are likely to succeed. Toward this end, we include a discussion of four cross-cutting issues: the definition of neural populations, trial-to-trial variability and Poisson-like noise, time-varying dynamics, and causality.https://jneurophysiol.podbean.com/e/jnp-micro-podcasts-four-questions-robert-kass/.Listen to this article’s corresponding podcast at  Neural circuits are described in terms of anatomical areas and subareas, including, when relevant, consideration of cortical structure within and across areas –6. AlthoSeveral useful overviews have appeared already, each with its own focus –25. SuchThe many ways that noisy data can provide evidence about the function of neural circuits are likely to be of interest to readers with a wide range of backgrounds; this includes a range of comfort with mathematically technical material. Although targeting an audience having a specific assumed level of familiarity with mathematical and statistical concepts would make exposition easier, we believe our overview can be of use to diverse readers. By emphasizing high-level motivations and concerns, we hope to indicate what the methods can achieve and the circumstances under which they are likely to succeed so that experimental investigators can identify scientific questions where these tools can be used to advantage. To maintain wide accessibility, we have chosen not to use mathematical equations. Without equations and more extensive explanations of procedures, those having technical backgrounds may find our very brief summaries inadequate, but rigorous definitions can be retrieved quickly from cited references and other sources.Point Process Models, we will not describe it in detail. Our aim, instead, is to direct readers to the underlying presumption that population bursts represent the propagation of information, the methods’ suitability for describing timing with millisecond precision, its use of a broadly applicable statistical framework involving latent variables, and the key components of the approach that apparently drive its ability to find strong representations of interaction.As an example of our presentation mode, we cite some of our own recent research, which began with the assumption, made by numerous studies, that behaviorally relevant information is transmitted across parts of the brain through transient bursts of activity in neural populations. If population bursts are indeed important, their timing should reveal coordinated activity: on a trial-by-trial basis, the time of a burst in one population should be related to the time of a corresponding burst in a downstream population. A study by Chen et al.  computedanalytic frameworks, between general statistical discussions in statistical models and important issues. In statistical models, we outline a few essential statistical concepts, including latent variables, which appear in many models of cross-population coupling to represent idealized, shared “drivers” of activity  distribution has a mean and standard deviation as parameters. When there are only a few parameters, a model may be relatively easy to understand but it restricts possibilities for data variation. On the other hand, when a very large number of parameters is used  models can be very flexible.theoretical instead of “population” for reasons articulated in the book by Kass et al.  is not freely ranging in a three-dimensional space; instead, it has two dimensions . This is the source of the terminology “degrees of freedom” in statistics. That kind of mathematical redundancy is not difficult to accommodate.Because parameters provide numerical labels to identify specific members of a family of probability distributions that make up a model, there is (for most standard models) a well-defined notion of the dimension of the model: it is the number of freely ranging univariate parameters used to identify a member of the family  was highly correlated with some combination of variables X2 and X3. In this case, it is common to introduce an empirical rule that uses some measure of correlation together with a threshold which, when exceeded, lumps the high correlation case together with exact mathematical dependence by deeming the collection  again to be lower dimensional. Similar reasoning applies when there are n variables having variation concentrated predominantly in a space of lower dimension k. Statistical redundancy arises in neural activity when the n recordings cannot vary separately in response to a stimulus or in contributing to behavior. This is analogous to finger kinematic redundancies during reaching tasks, where hand physiology constrains the fingers so that they cannot move independently . Factor analysis relies on similar reexpressions . It is easy to find good explanations of these methods, and basic intuitions appear in the article by Cunningham and Yu  random variables, just as X1 and X2 are independent when their correlation is zero, X1 and X2 become conditionally independent after conditioning on X3 when their partial correlation given X3 is zero  would be due entirely to the separate interactions of X1 with X3 and X2 with X3. Put differently, there is a dependence that is unique to the pair X1 and X3 and also to the pair X2 and X3, but there is no dependence that is unique to the pair X1 and X2.To highlight and clarify the distinction between pairwise and multivariate dependence, let us step through the case of three variables  is zero C. When tProbabilistic graphical models represent probabilistic dependencies, with Graphical models, graphical models can represent interesting dependence relationships across multiple populations. They are also a starting point for network analysis.Graphical diagrams such as those in undirected. When the edges are replaced by arrows, as in directed. Directed graphs are highly suggestive, but converting an undirected relationship based on correlation structure to a directed relationship requires additional information. In fact, it is not hard to create an example in which X1 and X2 being due to X3 the relationship is reversed: the combination of X1 and X2 produces X3, resulting in a graph as in X3. In neuroscientific applications, area-to-area arrows are generally based on some assessment of association  supplemented by consideration of timing. In most cases, however, arrows representing timing should be interpreted as predictive rather than causal, a point mentioned in Autoregressive models and Granger causality and discussed in Causality.The graphical models in X1 and X2 given X3 is much smaller than the original correlation of X1 and X2 (before conditioning on X3), the interpretation is that the separate interactions reflected in the statistical associations of X3 with X1 and X3 with X2 contribute substantially to the interaction reflected in the observed association of X1 with X2.Although only under rare circumstances can causal claims be justified based on partial correlation  in conjunction with timing information, they remain useful more broadly: when the partial correlation of X1, X2, X3 became summaries of activity in three populations for Chen et al.  from the many recordings in the other populations. This becomes a regression approach, illustrated in Fig. 3, A and B, but it is usually carried out using some form of generalized regression . A simpler possibility, for two populations, is to examine pairs of individual recordings, one in each population, for many pairs . Thus, LFPs are analyzed as time series. For point processes (Point Process Models), in theory, time is continuous, but in practice, spike trains are observed at discrete time values, with resolution such as 1 ms, so that the spike train data form binary time series (spike or no spike in each time bin). Similarly, in theory, Gaussian processes (GPs) (see Gaussian processes) are continuous, but they are applied to analyze time series of spike counts. A technical point is that a probability distribution for a stochastic process must specify all possible multivariate joint distributions, which leads to simplifying assumptions.In probability theory, a stochastic process (in time) is a collection of variables Especially important in population analysis is the idea that activity within a population may have a commonality conceptualized as a “hidden driver,” often considered to represent a “hidden state.” These are known as latent variables. The adjectives “latent” and “hidden” are used because latent variables do not correspond to any measured quantities; rather, they are theoretical abstractions introduced to construct a concise and intuitive model of covariation (see Ref. tZ becomes the high or low firing rate at time t and tY becomes the corresponding spiking behavior at time t (spike or no spike). Studies of neural variability sometimes examine theoretical firing rates instead of spike counts because the latter includes Poisson-like noise. The Poisson-like noise can be effectively reduced through the use of a statistical model that separates the theoretical firing rate from the Poisson-like noise and reports estimates of theoretical quantities, such as firing rate correlation instead of spike count correlation , it becomes a latent variable. A simple example is the use of “high” and “low” firing rates in a single-neuron model to capture bursting Ref. . In the relation , 48. Thirelation . We retuModels and parameters by restricting the variation of interest to a subspace of lower dimension than that of the observations themselves. Such dimensionality reduction is the purpose of factor analysis , where every measured variable is assumed to arise as a linear combination of some comparatively small number of latent variables , plus noise. In addition, PCA, and the closely-related canonical correlation analysis , can be derived as estimation procedures for latent variable models known as probabilistic PCA and CCA  is much smaller, which suggests identification of cross-population interactions per se ought to be more manageable.A prominent use of latent variable models is to provide a parsimonious representation of the redundancy in neural signals mentioned in hierarchical interactions. Here, we refer to statistical behavior rather than the widely discussed anatomical and physiological hierarchical structure of the cortex  would typically be considered nuisance parameters. For example, in their assessment of beta-frequency amplitude coupling between the prefrontal cortex (PFC) and visual area V4 during a visual memory task, the study by Bong et al. (Gaussian processes) treated the correlation structure among LFPs within each area as a high-dimensional nuisance parameter: even though the estimate of a general correlation structure among nearly 100 LFPs cannot be expected to be highly accurate, probable inaccuracies were considered unlikely to undermine the evaluation of cross-population coupling.Regardless of the modeling details, it is worth noting that when cross-population interactions are the focus of interest, parameters representing within-population interactions may be treated differently than parameters that identify cross-population interactions. In the statistical literature, necessary but uninteresting parameters are often called “nuisance parameters” . The data analytic techniques we describe may be considered, interpretively, to be ways of arriving at pictorial representations like those in In thinking about the many analytical approaches that can provide evidence for either correlative or predictive statistical dependence, it is important to remember that there are many ways multiple variables might interact, and as the number of variables grows it quickly becomes impossible to learn solely from data an accurate probability model that describes all the potentially complicated interactions. To make progress, some simplifying assumption is necessary. In the most common statistical contexts, it is assumed that all the variables are independent of each other: in this case, the probability density function for all of them together becomes the product of the individual-variable probability density functions. That, however, does not allow for statistical dependence . An intermediate simplification is to assume some form of conditional independence, as illustrated in The methods we summarize make use of these considerations: they are based on statistical models that define correlative or predictive relationships by imposing structure that often makes use of conditional independence . Our decomposition into six categories reflects in part the structure of the data and in part the relationships a method seeks to uncover. Autoregressive models, latent dynamic models, and frequency analysis  are all relevant to time series, i.e., substantial numbers of repeated measurements made at different times, sequentially, such as every millisecond (LFPs are time series). Point processes (the sixth category) are specific to spike trains and are especially valuable when precise timing of changes in firing rate could be important, so that counts in wide time bins might miss interesting effects. Time series can be analyzed by examining either behavior across time or oscillatory behavior for particular frequencies. Time-domain and frequency-domain methods are interrelated, sometimes they are used together, and sometimes time-domain methods consider particular frequencies whereas frequency-domain methods can involve dynamic evolution across time. Nonetheless, autoregressive models, latent dynamic models, and point process models emphasize time-domain methods.Within each category, we will list several main approaches and tools, but we can describe them here only very briefly. Some of the different methods may have different purposes as, we hope, will be clear. It is very common, however, to find several different statistical methods that claim to solve the same underlying problem because they impose different structural assumptions, as we will indicate; the choice among the alternatives becomes a judgment of which structures seem most relevant, or most intuitive, or most convenient in a given context. Our primary goal is to provide an organizational and conceptual view of the data-analytic questions being answered by available methodologies.X and those in the other by a vector Y and then finds the linear combinations of components of these vectors that have the greatest correlation, known as the canonical correlation; the vectors formed by the linear combination coefficients are the canonical vectors. When the canonical correlation is sufficiently large  this can give a definition for the connecting line in X and Y are vectors rather than scalars. The procedure is elaborated by removing from each of X and Y the variation due to their respective canonical vectors  and then treating the pair of residual variation vectors as before yielding a second correlation, which becomes the second canonical correlation, and a second canonical vector that is orthogonal to the first. The process may be repeated some number of times to produce Canonical Correlation Analysis (CCA). Semedo et al.  in two areas, an initial question is whether an increase in activity in one area tends to correspond to an increase in activity in the other. The simplest assessment of covariation across recordings, such as spike counts, from only two electrodes, one in each area, is the ordinary (Pearson) correlation. The existence of such a relationship is depicted in o et al.  used CCAo et al.  developeo et al.  extends Y and X and regressing Y on a dimension-reduced version of X. Ordinary least-squares regression finds the closest representation of Y within the space defined by linear combinations of the variables making up X (closest in the Euclidean sense of least squares). RRR takes the additional step of requiring the solution (defined by the X variables) to be of a lower dimension. Semedo et al. , treats the two areas asymmetrically, labeling the activity in the two areas by o et al.  used RRRo et al. . Partialurchland  suggesteIn applying these linear multivariate techniques, a concern, ubiquitous in statistics, is the inherent arbitrariness in the choice of a criterion that produces a method. In the case of canonical correlation, the maximization of correlation is clearly simple and intuitive, but should not be considered compelling. On the other hand, for the communal enterprise of science, there are big advantages to using well-established methods. Similarly, although linearity is, in principle, restrictive, the noisiness of the data together with modest sample sizes often precludes the identification of nonlinear relationships, and even when some nonlinearity is detected, its effect on results may not change conclusions.Latent Variables and illustrated in Gaussian processes  given all the variables represented by all the other nodes. The simplest case was discussed with reference to Causality. With this reality in mind, the construction of a Gaussian graphical model may be considered a way of estimating a variance matrix. When the matrix is large it is difficult to estimate accurately (because of the cumulative effects from inaccurate estimation of large numbers of correlations), and setting many partial correlations to zero  effectively removes many of the parameters and can stabilize estimation. Vinci et al.  are not scientifically meaningful for a specified purpose, a point we repeat in i et al.  combinedi et al. , in theiIn analyzing recordings across many populations, each node might signify an individual recording, or a population summary of them, or a latent variable representing a population summary. For example, to analyze LFP beta oscillations recorded from 24 electrodes across PFC and the hippocampal areas dentate gyrus (DG), subicullum (Sub), and CA3 during a memory retrieval task, Klein et al.  developeFrequency Analysis, we will say more about the methods used in In X1, X2, X3,… at times t = 1,2,3,…, is Granger causal of a time series of values Y1, Y2, Y3,… if, for every time value t, the past of tX  is predictive of tY, after taking account of the inherent dependence of tY on its own past. One of the first studies that applied Granger causality to LFPs, Brovelli et al.  and, second, that the activity in some areas predicted activity in other areas .An important method for identifying interactions across areas from LFPs is Granger causality , 70. Thei et al. , demonsttY at time t, is said to be autoregressive if there is a regression (a nonzero regression) of tY on t −Y1, for all values t. This concept applies to stationary time series, meaning those having probability distributions that are time-invariant  models extend this concept to multiple time series.The formal definition of Granger causality involves autoregressive processes, which are important in their own right. A time series taking values tX is Granger causal of a time series of values tY if the regression of tY on the values t −Y1, t −Y2,…, t − pY together with the values t −X1, t −X2,…, t − pX is stronger than the regression of tY on t − Y1, t − Y2,…, t − pY alone. This verbal summary is meant to provide a succinct description of the concept of theoretical stationary time series; there are many important details in implementation and practice, and cautionary concerns about the application of Granger causality appear under time-varying dynamics, below. In addition, Granger causality is something of a misnomer because, as we discuss in Causality, it is rarely causal in the usual scientific sense.With this in mind, a time series of values There are extensions of Granger causality based on directed information –74, as wt in terms of states and noise at time t may be designated in the general form,Stochastic Processes) within what is usually called a “state space.” The first line is often called the observation model while the second line becomes the state model. Important special cases are linear dynamical system models , latent Gaussian process models, and the many generalizations of these two special cases; we give a few pointers to relevant literature in three successive subsections  takes values often known as states, which evolve dynamically, across time. The latent state variable represents theoretical quantities of interest, and its path across time is estimated from observations, often with the goal of prediction. The framework for observation at time In theory, stochastic processes can be used to formulate continuous-time state-space models but practical implementations revert to discrete time. Although this may make the distinction between discrete and continuous time seem unimportant, some formulations have origins, and, thus, intuitions and useful results, grounded in continuous time. Models that are inherently discrete, and typically have additional structural simplifications, are usually called state-space models. When “combines … with” involves linear models , the modifier “linear” may be included but, because this special case is so common, it is frequently taken as a default with “linear” omitted.In neuroscience, state estimation is often known as “decoding,” with “encoding” referring to the process of estimating unknown parameters in the model, such as those appearing in the linear transformations and the noise distributions, see dynamical system that evolves in continuous time, moving from a state at time t to another state at time t′, according to differential equations, without being stochastic as it is in In applied mathematics, the term “state space” is synonymous with “phase space,” where it refers to the possible configurations of a In state-space models, the probability that a latent variable will be in a specific state at a particular time is typically restricted to depend on the most recently occurring state but not on earlier states (which is known as a Markov assumption). When the form of combination in t1 and t2. To make analysis tractable, GP technology has emphasized particular forms of covariance, which restrict the appearance, especially the smoothness, of the resulting trajectories. Yu et al.  similarly to, though differently than, Poisson-based or point process models.A Gaussian process (GP) is a stochastic process in which all the multivariate joint distributions are Gaussian. This requires specification of the covariance of variables u et al.  replacedu et al. A with Gau et al. C and shou et al.  allowed Gokcen et al.  extendedHigh dimensionality in the Defining Neural Populations section), and they applied the methods to find time-varying beta amplitude coupling between PFC and V4 during a visual memory task.Bong et al.  and 65 ulatent drivers (they drive the population activity), and then let us refer to the different dynamic regimes as being in alternative states. With this terminology, SLDS models are called recurrent (rSLDS) if the latent drivers influence the probability of being in a particular state. A series of papers have developed these for spiking data. Glaser et al. (The linear-Gaussian (or LDS) model and accompanying methodology have been extended widely, demonstrating the depth and breadth of the latent dynamical modeling framework  to involve neural network models. Gao et al.  showed hLatent drivers and hierarchical interactions.Neural networks may be especially valuable when they can be used in hybrid models that incorporate components involving interpretable parameters together with components for mapping functions  that do not require interpretation. The neural networks would then involve high-dimensional nuisance parameters in the sense of our preliminary remarks in Interest in neural oscillations has a long history .In the same sense that coherence is analogous to correlation, partial coherence . Under that model, when maximum likelihood estimation of the latent correlation matrix is applied to narrowly band-pass filtered data, each correlation becomes a latent coherence, while each partial correlation becomes a latent partial coherence . One of the data analytical results is displayed in Urban et al.  used theGaussian processes in the Latent Dynamic Models section, Bong et al. . In practice, spikes are recorded in small time bins, and if the bins are small enough that at most one spike can occur in each bin, the point process defines a bin-specific probability that a spike will occur and the spike count (0 or 1) in each bin may be considered to follow a Poisson distribution. Because of possible statistical dependencies across bins, the spike counts in larger time bins need not be Poisson, and statistical point process models can mimic a wide variety of spiking behavior, including the Poisson-like yet discernibly non-Poisson behavior of observed spike trains that are commonly observed in vivo in the cortex –122.1) a simple, universal formula for the probability density of the spike train in terms of the theoretical firing rate and 2) a specification of the way the theoretical firing rate depends on relevant variables. The variables determining the theoretical firing rate could include measurements characterizing the stimulus, or behavior, or the past spiking of the neuron itself or other neurons, and it often becomes a latent variable (as discussed in Latent variables). Point process models are typically implemented using standard generalized regression methods  and fitting population firing rate functions separately for each experimental condition based on condition-specific neural populations. They used the simpler approach to analyze the mouse-to-mouse variation of peak times and the correlation of peak times across seven brain areas. Additional, related, unpublished work by Xin, Siegle, and Kass demonstrates ways in which population firing rate coupling models can be much more accurate than individual neuron models for identifying cross-population interactions, and they use population firing rate models to document strong diminution of particular interactions across visual areas during locomotion.As yet unpublished work by Olarinre, Siegle, and Kass used a simpler approach than that of Chen et al. , corroboEvery statistical model has assumptions, and every analytic method highlights some features of the data while ignoring others. We have not listed the many caveats that accompany each approach. In this section we make cautionary remarks, confining them to a few points that may be easily overlooked or ignored.In spike train analysis, the sampled neurons are inhomogeneous, with both excitatory and inhibitory cells varying in properties, genetic makeup, location (including depth in the cortex), and function . TypicalLocal field potentials also arise from many diverse sources, which may have very different activation patterns. One approach to disentangling the signals is through current source density localization , 140, meWhile large numbers of electrodes create great opportunities to attack complexities in cross-population coupling, they also create computational challenges, which a small body of work has addressed , and the small effects are not important. In settings such as linear regression and generalized regression, this leads to a computationally efficient and well-studied method known as L1 regularization, often called Lasso, which reduces the size of parameter estimates (it “shrinks” them) and sets the smallest estimates to zero. L1 regularization has been used to analyze multiple simultaneously-recorded spike trains where a given neuron’s spiking behavior could be functionally related to the spiking behavior of large numbers of other neurons  but rather a large number of small effects. This calls into question the assumption of sparsity. In addition, statistical inference with L1 regularization can be challenging. Two ideas have been used to improve the situation. First, it is known that Lasso is generally better at prediction (predicting the firing rate of one neuron based on firing patterns of many others) than model selection (finding correctly the set of neurons that have strong interactions with a given response neuron): intuitively, a good set of “wrong” variables can predict nearly as well as the right ones ; see the discussion by Bühlmann . Bong etGraphical Models, where the usual L1 regularization for variance matrix estimation known as the graphical Lasso was modified by allowing the shrinkage of partial correlation for each pair of firing rates to depend on the distance between the two neurons and their tuning curve correlation. This produced the striking improvement in performance shown in Often, special-purpose methods can improve on generic Lasso-based approaches by incorporating scientifically reasonable assumptions. This was the strategy of Vinci et al. , discussTraditionally, interactions across brain areas have been depicted as static network snapshots. In reality, brain networks are dynamic and constantly changing. In many situations, the changes across time are of central interest. Tracking such changes is the primary motivation not only for the peristimulus time histogram (PSTH), but also for comparatively recent methods such as GPFA.A particular challenge, affecting both spike trains and LFPs, is large fluctuations driven by stimulus or behavior, often called evoked or transient (or phasic) responses, which are clearly visible in typical PSTHs and trial-averaged LFPs. Such pulsatile fluctuations are difficult to reconcile with the statistical assumption of stationarity (time invariance), which is fundamental to common time series procedures. Repeated trials can provide the information needed to disentangle transient fluctuations from the kind of steady-state variation standard time series methods are built to handle. In GPFA, multiple processes with different effective timescales can often accommodate transient fluctuations while also capturing background variation. However, application of Granger causality requires care, and must be modified or abandoned in the presence of transient activity , 148. ThAt the opposite end of the spectrum, a variation that is slow relative to the length of the trial creates what is known as long-range dependence, which also causes problems. In time series models, the dependence between observations at different points in time, often measured by their correlation, which in this context is called autocorrelation, tends to get smaller as the time between the two observations increases. When the autocorrelation function decays exponentially fast, the dependence is called “short range,” and when it instead decays slowly the time series exhibits “long-range dependence.” Even though long-range dependence can satisfy stationarity, when long-range dependence is present typical time series procedures will behave poorly, producing effects that are similar to nonstationarity . If, forf noise,” by which it is meant that the spectral density (the power spectrum), written as a function of frequency f, decreases either exactly or approximately as 1/f, though the terminology often refers to decreases that have a more general power law form 1/f α, with α not necessarily close to 1. The exact or approximate form 1/f contrasts with spectra that decrease at least as rapidly as 1/f2, which are seen in standard statistical models exhibiting short-range dependence, such as autoregressive models and the most commonly-applied Gaussian process models, all of which would be considered “well-behaved.”A conceptual complication, which often produces some confusion, involves the characterization of signals exhibiting long-range dependence as “1/f” may refer to any or all of three statistically different cases: exactly 1/f, approximately 1/f, or more general power law cases (including 1/f2). Second, when a time series appears to exhibit long-range dependence it is difficult, statistically, to determine the precise decay rate of the spectral density. Third, there are several phenomena that may or may not accompany and explain long-range dependence, including scale invariance, chaotic evolution, and self-organized criticality. More specifically, there are many ways to generate time series having spectra that decrease as 1/f α, including the special case α = 1. In particular, beginning with a Poisson process that produces decaying voltage pulses, as in the usual conception of synaptic input, various realistic considerations  can lead to exact or approximate 1/f α spectra, with the value of α depending on the precise specification  and LFPs . Trial-to-trial variation is often called “noise,” especially in the context of spike count correlation , 155. A Point process models, meaning that spiking patterns are similar to those produced by a Poisson process; although close examination typically reveals them to be noticeably different, neural spiking patterns are often not far different from patterns produced by Poisson processes  when values of X change , while all of the inputs to the neurons whose activity is represented by Y (those inputs that are not themselves driven by X) remain the same. Because it is not possible to observe neural activity Y under “exactly the same brain activity configurations” for two different values of neural activity X, a comparison of them involves potential outcomes, which are also called “counterfactual.” Statistical causal analysis thus defines causal effects in terms of potential outcomes, and under special circumstances characterizing the design of a study  it is possible to obtain causal statements  the measurements adequately represent relevant population activity and 2) no other brain areas affect this relationship, it is extremely difficult to distinguish a small partial correlation from a zero partial correlation, and the usual interpretation of One of the difficulties, mentioned in Causal manipulation can be provided by optogenetic stimulation, which has been a spectacular advance, yet requires care to avoid misleading results , 165. Onacyclic graphs (DAGs), which means they do not contain paths leading from a node through other nodes and back to the starting node. This restriction of causal graphs to DAGs rules out recurrent relationships.Causal effects are often depicted using directed graphs. An important caveat, however, is that in representing causal effects based on causal analysis, the directed graphs are restricted to being directed Our guide for data analysts wishing to identify interactions among neural populations has stressed analytical frameworks and statistical issues because progress requires both deployment of effective data analysis tools and appreciation of their inferential roles. There is a tension here, however, between powerful methods on the one hand, and a series of statistical caveats, on the other, caveats that can sometimes seem dishearteningly conservative especially when contrasted with the more ambitious culture of computer science that dominates machine learning .Causality, causal statements are said to concern “effects of causes” as opposed to “causes of effects.” Although the most important issue in causal reasoning, the potential influence of confounding variables, arises repeatedly in many contexts, it is, at least conceptually, widely appreciated by experimental investigators and is often addressed as a key discussion point in scientific reports. In addition, the flip side of the effects-of-causes versus causes-of-effects dichotomy is that the effects of causal manipulations resulting from the “gold standard” of randomized controlled trials, while crucial, are rarely fully satisfactory for scientific pursuit. This is clearest in clinical studies. For example, randomized controlled trials demonstrated the effectiveness of lithium in treating bipolar disorder long before the emergence of substantial knowledge about potential mechanisms and, while evidence of effectiveness has strengthened (The prevailing agnosticism of statistics toward theoretical implications of data-driven results is most apparent in statistical causal analysis where, as described in ngthened , even nongthened . It is tngthened  and 175.ngthened , will suMore generally, scientific articles often devote considerable space to post hoc explanatory hypotheses, stories that aim to synthesize and interpret results in terms of presumptive causal mechanisms. Such narratives are essential, even treasured components of the process. Still, it is important to recognize them as speculating about causes of effects, which is different from stating accurate interpretations of observed results. Scientific conclusions must combine preexisting knowledge and assumptions with data analyses based increasingly on advanced methods that involve subtleties of reasoning. This was a major motivation for our emphasis on statistical issues. As emerging technologies create more refined and detailed data, the concepts invoked here will likely endure by suggesting principled paths toward new methodologies.This work was supported by National Institute of Mental Health and Neurosciences Grant RO1 064537.No conflicts of interest, financial or otherwise, are declared by the authors.R.E.K. conceived and designed research; H.B., M.O., Q.X., and K.U. analyzed data; H.B., Q.X., and K.U. prepared figures; R.E.K. drafted manuscript; R.E.K. edited and revised manuscript; R.E.K., H.B., M.O., Q.X., and K.U. approved final version of manuscript.


In June 2020, a staff-led open letter containing more than 1,100 signatures and 200 testimonies of abuse and discrimination went public [A torrent of public attention has surfaced myriad allegations of exploitation, discrimination and abuse by humanitarian, development, international aid, and global agencies. Amid these, Médecins Sans Frontières (MSF), our former employer, has been thrust into the spotlight, owing in large part to the t public .Calls to ‘decolonise’ global health by academics, practitioners, activists, and students differ in their approach and focus. While they jointly seek to address and dismantle racist and discriminatory structures and norms, few have delved into the more complex analysis of the “monopoly, misuse, or abuse” of power , includiAbuse–be it in the form of retaliation or rape, derogatory comments or discriminatory contracts, nepotism or neglect–stems from systemic asymmetries that foster, invite, and enable the misuse of power and dominance. Abimbola et al have explored facets of supremacy, encompassing coloniality, patriarchy, racism, white supremacy and saviorism, that together maintain power and privilege within global health . These fDignity at MSF in September 2021, a movement-wide report on abuse and discrimination based on findings of an online survey with 359 current and former staff and stakeholders [As Decolonise MSF organisers, we contributed to urgent demands for structural reform and transparency by publishing eholders . It is tMSF’s external accounting on abuse focuses on a relatively small number of formal complaints logged each year with ethics and behavioral units . Our resThe New Humanitarian stipulated that MSF lacks data for the one-year period since May 2020 on changed human resources practices and does not report on the percentage of leadership coming from under-represented groups [These results are difficult, if not impossible, to contextualize because aid organisations rarely measure–or disclose–abuse or discrimination perceived by their workforce. Often there is no baseline: 2020 marked the first in MSF’s 50-year history in which it compiled formal complaints from global offices in addition to those from medical projects in the field . As reced groups .In a context of inaccessible information on matters of the public interest, effective activism may require the direct production of research, even with limited means and methodological weaknesses, to advance understanding and future action when an institution cannot, or will not, study these questions. Such research may therefore be considered inherently agitational, requiring a mutual responsibility for diligence and safety by organisations and activists. Our report–created with free resources and volunteer labour–openly acknowledges its limitations, including possible self-selection despite our expansive outreach, ambiguities in question phrasing, our inability to verify employment status, and the lack of a suitable peer reviewer. We were not officially authorized to do this work but chose to disclose our authorship to promote full transparency and feedback. We nonetheless had to carefully navigate a maze of painstaking efforts to minimize our own legal and professional risks, including attacks by current MSF stakeholders and continual revision to ensure our report wording could not be framed as defamatory.the researcher and researched. Critically engaged activist research “provides an important approach to addressing the practical and ethical dilemmas of knowledge production” [This type of research forces us to query the assumptions coded into the roles of duction” . It confduction” .As survivors of abuse within the organisation, we would argue that our lived experience–our entanglement–allowed us to formulate specific questions currently not captured by the institution, gain necessary trust, and better level power imbalances intrinsic to research processes. Our reflexivity served a process to unknot how power manifests towards and through us as individuals and institutions, resulting in a re-examination of the classical research model itself. Global health transformation requires relatable and personal discourse through reflexive dialogue between individuals across geographic, economic, and epistemic divides . The repAs former staff with racialized backgrounds employed on international contracts, we have tried to embrace our “responsibility to speak up commensurate to position and privilege” . Our repDignity at MSF represents activist research in the spirit of the “generative power of protest”, which recognizes the “power of protest events themselves to shape internal movement dynamics” [If it succeeds, ynamics” . In our


Forming long-term intimate relationships is a human universal, with most people across different times and cultures doing so. Such relationships should be associated with important benefits otherwise individuals would not engage in them, with the current research aiming to identify what people consider as beneficial in a long-term intimate relationship. More specifically, Study 1 employed qualitative research methods in a sample of 221 Greek-speaking participants, and identified 82 perceived benefits. Study 2 employed quantitative research methods in a sample of 545 Greek-speaking participants, and classified these benefits into 10 broad factors and two broader domains. Experiencing positive emotions, including love and passion, as well as having someone to provide support and do things together, were considered among the most important benefits. Although there were a few significant differences, the evaluations of the perceived benefits of intimate relationships were generally consistent across participants of different sex, age, and relationship status. Across different times and different cultures, people form long-term intimate relationships , which sHuman mating is strategic in the sense that people employ specific strategies in diverting their resources toward achieving specific mating goals . ChildreThese selection pressures have resulted in long-term mating to be the most prevalent mating strategy, with different lines of evidence supporting this prediction. In particular, sexual dimorphism exists within a species when the sexes differ in size or appearance , with li1). That is, people would consider it beneficial to enter into an intimate relationship, because by doing so, they would get an intimate partner who would provide them and their children with reliable support, and would be there for them in times of need. The fitness benefits of long-term intimate relationships would favor the evolution of mechanisms such as emotions (2).The above theoretical framework indicates that one major survival and reproductive or fitness benefit of long-term relationships is to have someone around who would provide reliable support and protection (Hemotions  that wouemotions . Accordi3). Emotional adaptations are proximate mechanisms that serve the ultimate goal of propagating the genes that code for their ontogenetic development. One way to achieve this goal is to generate emotional responses that motivate the formation of long-term intimate relationships, which have important fitness advantages. Positive emotions and sexual satisfaction are indirect fitness benefits, that is, they do not directly increase fitness the same way as receiving support from a partner does, but do so indirectly by motivating people to form lasting intimate relationships in order to enjoy them. The existing literature provides some support for these hypotheses.In the same vein, sexual desire mechanisms would motivate people to seek intimate partners in order to have regular sexual contact . AccordiSeveral studies have found that marriage is associated with benefits including physical health and longevity, mental health and happiness, economic well-being, children performing better , and higher sexual satisfaction  and keeping one.In more detail, Study 1 employed qualitative research methods in order to create an inclusive list of what people consider beneficial in being in a long-term intimate relationship, and Study 2 employed quantitative research methods in order to classify these benefits into broader categories. We hypothesize that these categories would reflect three main benefits namely, having someone around to provide support and protection, enjoying positive emotions, and having regular sex. Nonetheless, our study is explorative, as the complexity of the phenomenon and the limited research in the area, prevents us from forming hypotheses for all possible benefits of being in an intimate relationship. In addition, in order to examine whether men and women and people in different age and relationship status groups viewed the benefits of intimate relationships differently, we examined sex, age, and relationship status effects, without however making directional hypotheses.SD = 10.2), and the mean age of men was 28.2 (SD = 11.1). With respect to the relationship status, 24.2% of the participants indicated that they were involuntarily single, 23.7% in a relationship, 17.6% voluntarily single, 13.1% in single-between relationships, 12.3% married, and 9.1% indicated their relationship status as “other.”The study was conducted at a private university in the Republic of Cyprus and has received ethics approval from the institution's ethics board. Participants were recruited by promoting the link of the study on social media , and by forwarding it to students and colleagues, asking them to forward it further. The only requirement for participation was to be at least 18 years of age. Participation was on a volunteer basis, and no monetary or other incentives were given. Overall, 239 individuals took part in the study. Yet, in order to increase validity, we excluded participants who indicated that they were currently single and had never been in a relationship before. In effect, we analyzed the responses from a sample of 221 Greek-speaking individuals . The mean age of women was 27.8 .For the purpose of analyzing our data, we recruited two independent graduate students (a man and a woman). Each research assistant was asked to go through the responses and prepare a list of benefits associated with being in an intimate relationship. The assistants were instructed to eliminate answers with unclear or vague wording. After processing about 30% of the responses, they discussed and compared their respective lists of benefits, and then moved on to process the remaining responses. Two lists of benefits, one from each assistant, were produced and were compared with each other. Agreement was found for most of the items. In cases where there was no complete overlap, the authors were consulted, and eventually, all the parties involved agreed to a final list of benefits. In total, 82 benefits were identified and are presented in SD = 11.2) and the mean age of men was 32.3 (SD = 12.1). In addition, 38.2% of the participants indicated that they were in an intimate relationship, 20.0% single without wanting to be so, 14.5% between relationships, 12.7% married, 7.0% single by choice, and 7.7% indicate their relationship status as “other.”In order to recruit participants, we employed the same method as in Study 1. Overall, 583 individuals took part, but in order to increase validity, we excluded the answers of those who indicated that they were currently single and had never been in a relationship before. In total, 545 (299 women and 246 men) Greek-speaking individuals took part. The mean age of women was 30.6 , which was also entered as an independent categorical independent variable. In order to do so, we collapsed all the singlehood categories into one , the “in a relationship” and the “married” into one , and we retained the “other” category.In total, 10 factors were extracted and are presented in Moving on, participants indicated that one benefit of intimate relationships was to experience “Positive emotions,” including joy, optimism, and warmth. In the “Give and receive care” factor, one benefit people indicated was to have someone to care for as well as to have someone to care for them. The “Safe sex” and fewer chances to contract a sexually transmitted disease, were also considered beneficial in an intimate relationship. In addition, experiencing “Love and passion” factor, as well as companionship and affection, were indicated as benefits. Furthermore, in the “Sharing expenses” factor, participants indicated that one benefit of being in an intimate relationship was to have someone to share expenses and obligations. Lastly, participants indicated “Stability” to be another benefit of being in an intimate relationship.Means and standard deviations were calculated for each factor and are placed in a hierarchical order in In order to classify the identified factors into broader domains, we performed second-order factor analysis by applying principal axis factoring using the direct oblimin as the rotation method on the 10 extracted factors. The results indicated a two-domain solution. As we can see from M = 4.32, SD = 0.75) than those who were single  or who have indicated their marital status as “other” .In total, 10 MANCOVA tests were performed. Thus, in order to avoid the problem of alpha inflation, Bonferroni correction could be applied, setting the significance level to .005 (.050/10). As we can see from In the current research, we identified 82 possible benefits of being in a long-term intimate relationship, which were classified into 10 categories reflecting broader benefits, which in turn, were classified into two domains reflecting intrinsic and extrinsic benefits. Among the most important ones, were experiencing positive emotions, including love and passion, as well as having someone to provide support and to do things together. Although there were some significant differences, the evaluations of what was considered beneficial in intimate relationships were generally consistent across participants of different sex, age, and relationship status categories.As we originally predicted, people considered having someone to provide them with “Support,” as a crucial benefit of being in an intimate relationship. This factor was rated third in importance, with about 93% of participants considering it beneficial. The “Give and receive care” factor, found in the middle of the hierarchy of importance, is to some degree consistent with this argument, as participants considered it beneficial to have someone to look after them. Likewise, the “Sharing expenses” factor, with participants indicating as a benefit of a relationship to have someone to share expenses and provide financial support, is also consistent with this prediction. Yet, this factor was second from the bottom in the hierarchy of benefits, with about 42% of the participants considering it important. In our hypothesis, people would consider the support they receive from their partners beneficial also for their children. Nevertheless, participants did not specifically reported that one possible reason being that they used the term “support” more broadly, and inclusive of supporting one's children.Also consistent with our original hypothesis, participants indicated experiencing “Positive emotions,” and “Love and passion” in particular, as benefits of being in an intimate relationship. These two factors topped the hierarchy of importance, with more than 95% considering “Love and passion,” and more than 94% considering “Positive emotions,” as important benefits of being in an intimate relationship. Nevertheless, there was no specific factor indicating the avoidance of negative emotions as a benefit of intimate relationships. Yet, the “Have someone to keep me company and to do things together” factor, had such a facet: Participants indicated as beneficial of a relationship to have someone to keep them company so that they do not feel lonely. Furthermore, as we originally predicted, receiving “Sexual satisfaction,” involving regular and easier sex, emerged as benefit of being in an intimate relationship. This factor was found at the middle of the hierarchy of importance, with about 86% of the participants rating it as such.Several factors emerged, which we have not originally predicted. To begin with, participants indicated the “Have someone to keep me company and to do things together” to be an important benefit of intimate relationships. People have a basic need to receive social input that is, to have around them others with whom they could interact, share their thoughts, and discuss what troubles them . An intiMoreover, people indicated “Safe sex” to be another important benefit of being in an intimate relationship. This factor probably reflects increasing awareness of the causal link between having sex with different partners and the increase in the probability to contract a sexual transmitted disease, as well as the health risks associated with these diseases. For instance, it has been shown that, by increasing the costs of multiple mating, sexually transmitted diseases have favored relatively monogamous mating strategies . In addiFemale participants tended to rate the benefits of intimate relationships higher than male participants, with this tendency passing the significance level in three instances. The largest sex difference was over the “Give and receive care,” followed by the “Love and passion” factor. This finding could be interpreted to mean that men consider being in a long-term intimate relationship less beneficial than women. One possible reason is that, by virtue of not having to bear the burden of pregnancy, men can receive more reproductive benefits from short-term intimate relationships than women , and theSignificant age effects were found for the “Positive emotions” and the “Give and receive care” factors, with older giving lower scores than younger participants. These findings may be interpreted to mean that emotional responses to intimate relationships as well as the need to give and receive care, are stronger in younger people. Moreover, for the “Social acceptance factor,” the age effect was very close to the Bonferroni-adjusted significance level, with older participants giving higher scores than younger ones. One reason could be that, as people get older and remain single, their friends and family worry more that they will remain unmated forever, and increase thus, their pressure on them to get an intimate partner. In effect, older people would find it more beneficial to be in an intimate relationship in order to gain social acceptance. Moving on, people who were in an intimate relationship rated the “Support” factor higher than people who were single, one possible reason being that, the support they received from their partners, made a noticeable difference in their lives see also . In geneThe observed domain structure indicates that, when people reflect on what is beneficial in a long-term intimate relationship, they consider primarily intrinsic benefits (the factors which loaded in this domain had the highest means), such as experiencing positive emotions, and secondary, the extrinsic benefits of it, such as relaxing social pressures. The “Love and passion” and the “Positive emotions” factors had the highest loading on the “Intrinsic benefits” domain, and the highest means among the identified factors. It is reasonable to assume that, what people consider beneficial in an intimate relationship, would motivate them to enter in one. In this respect, our findings suggest that people would be motivated to form a long-term intimate relationship primarily in order to experience positive emotions such as love (regarding the importance of love at the beginning of the relationship see What is considered beneficial in an intimate relationship, depends on the traits and circumstances of the individual. For instance, people who are well-off, may not consider a particularly beneficial of a relationship to have someone to share expenses, with the opposite being true for people who face financial difficulties. People who have a more independent personality, may value factors such as “Support” and “Have someone to keep me company and to do things together” less than people who have a more dependent personality. People who score high in agreeableness and enjoy helping others may value more the “Give and receive care” factor than low scorers. Accordingly, future research needs to identify which individual differences predict how people value the different benefits of being in an intimate relationship. Such endeavor would enable us to better understand how individual differences relate to relationship formation as well as to relationship quality see .How people value the different benefits of being in an intimate relationship would be also affected by cultural variables. For instance, in the Greek cultural setting, parents are proactive in motivating their children to enter in an intimate relationship, which suggests that, in this context, the “Social acceptance” benefit would be considered more important than in other cultural contexts where parents are less involved in mate choice. Similarly, people living in countries where there is only limited awareness of sexual transmitted diseases may consider the “Safe sex” benefit as less important than people living in countries where there is higher awareness. Thus, cross-cultural research is necessary in order to identify how cultural variables affect variation in how people assess the different benefits of being in an intimate relationship see .Our study examined the perceived benefits of being in an intimate relationship, which do not necessary completely overlap with the actual benefits of being in an intimate relationship. For instance, studies consistently find that being in an intimate relationship is associated with important health outcomes e.g., ; yet, inFurthermore, we have argued that having a long-term intimate partner has been associated with important benefits during human evolutionary time; yet, because modern conditions are different from ancestral ones, these benefits are likely to be different see also . For insOn the other hand, it could be counterargued that, in contrast to ancestral human societies, people today live in large cities, surrounded by people they do not know and with whom they are not related. Accordingly, a long-term partner could be a valuable source for receiving social input, as well as support with everyday challenges. Similarly, although it is true that modern technology gives the opportunity of having a child without having an intimate partner, due to the high cost involved, access to this technology is beyond the reach of most people. Moreover, although welfare systems can support one-parent families, in most countries such support is far from adequate to cover a family's needs . In addiOne limitation of the current work is that it was based on non-probability samples, so its findings may not readily generalize to the population. Additionally, we employed self-report instruments which have several limitations, including participants not giving accurate answers. Moreover, our study was confined to the Greek cultural context, and its findings may not apply to other cultural settings. In addition, we focused on long-term intimate relationships; yet, forming short-term intimate relationships, is also part of the repertoire of human mating , and whaForming lasting intimate relationships constitutes a central aspect of human behavior. In the current research, we identified several perceived benefits of intimate relationships. Future studies that would employ different and more diverse samples, would enable us to better understand what people consider beneficial in being in a long-term intimate relationship.