Salience Network and Default Mode Network dysfunction after traumatic brain injury

It is now widely accepted that cognitive control depends on the integrated operation of large-scale distributed brain networks. Recent methodological advances allow both structural and functional connectivity (FC) within these networks to be studied non- invasively in vivo. These approaches hold the promise of dramatically extending our understanding of the impact of traumatic brain injury (TBI) on cognitive control, which has the potential to help determine strategic targets for the rehabilitation of individuals with TBI. In the current thesis, structural and functional magnetic resonance imaging is combined to test the general hypothesis that cognitive deficits after TBI arise from functional disconnection within brain networks that mediate cognitive functions. Of particular interest are the interactions between two brain networks known as the Salience Network (SN) and the Default Mode Network (DMN). These networks are thought to be important for cognitive control however, how these networks interact during cognitive control is limited. This thesis largely investigates the effect of TBI on network interactions that accompany changing motor control. Functional MRI of the Stop Signal Task (SST) is initially used to study response inhibition. In healthy subjects, FC between the right anterior insula (rAI), a key node of the SN, and the DMN transiently increased during stopping. This change in FC was not seen in a group of TBI patients with impaired cognitive control. Furthermore, the amount of damage to the underlying white matter tract negatively correlated with the strength of FC between the networks. These findings are confirmed in a second group of TBI patients. In the second group, switching rather than inhibiting a motor response: (1) was accompanied by a similar increase in network FC in healthy controls; (2) was not seen in TBI patients; and (3) tract damage after TBI again correlated with FC breakdown. I also replicate this pattern of structure-function in a group of elderly participants who demonstrate similar cognitive control impairments as the TBI group. The findings show that FC between the rAI and DMN increases with cognitive control, and that the ability to efficiently regulate the FC between the rAI and DMN can be predicted by the structural integrity within a remote brain network previously proposed to be involved in switching between internally and externally directed attention. This work provides evidence for a model of cognitive control where the SN is involved in the attentional capture of salient external stimuli and signals the DMN to reduce its activity when attention is externally focused. It also identifies DMN dysfunction as underlying various cognitive deficits after TBI, and confirms the relevance of white matter damage in the development of brain dysfunctions after TBI

The impact of patient involvement on participant opinions of information sheets

Background Patient and public involvement (PPI) groups can provide valuable input to create more accessible study documents with less jargon. However, we don't know whether this procedure improves accessibility for potential participants. Aims We assessed whether participant information sheets were rated as more accessible after PPI review and which aspects of information sheets and study design were important to mental health patients compared with a control group with no mental health service use. Method This was a double-blind quasi-experimental study using a mixed-methods explanatory design. Patients and control participants quantitatively rated pre- and post-review documents. Semi-structured interviews were thematically analysed to gain qualitative feedback on opinions of information sheets and studies. Two-way multivariate analysis of variance was used to detect differences in ratings between pre- and post-review documents. Results We found no significant (P < 0.05) improvements in patient (n = 15) or control group (n = 21) ratings after PPI review. Patients and controls both rated PPI as of low importance in studies and considered the study rationale as most important. However, PPI was often misunderstood, with participants believing that it meant lay patients would take over the design and administration of the study. Qualitative findings highlight the importance of clear, friendly and visually appealing information sheets. Conclusions Researchers should be aware of what participants want to know about so they can create information sheets addressing these priorities, for example, explaining why the research is necessary. PPI is poorly understood by the wider population and efforts must be made to increase diversity in participation

Investigating patient acceptability of stratified medicine for schizophrenia : a mixed methods study

Background Health services have advocated a stratified medicine approach in mental health, but little is known about whether service users would accept this approach. Aims To explore service users’ views of the acceptability of stratified medicine for treatment-resistant schizophrenia compared to the traditional “trial-and-error” approach. Methods A mixed methods observational study that explored questionnaire responses on acceptability and whether these responses were affected by demographic or clinical variables. We also investigated whether treatment responsiveness or experience of invasive tests (brain scans and blood tests) affected participants’ responses. Questionnaire generated qualitative data were analyzed thematically. Participants (N108) were aged 18–65, had a diagnosis of schizophrenia, and were adherent to antipsychotic medication. Results Acceptability of a stratified approach was high, even after participants had experienced invasive tests. Most rated it as safer (62% vs 43%; P < .01 [CI: −1.69 to 2.08]), less risky (77% vs 44%; P < .01 [CI: −1.75 to 1.10]), and less painful (90% vs 73%; P < 0.01 [CI: −0.84 to 0.5]) and this was not affected by treatment responsiveness or test experience. Although not statistically significant, treatment nonresponders were more willing to undergo invasive tests. Qualitatively, all participants raised concerns about the risks, discomfort, and potential side effects associated with the invasive tests. Conclusions Service users were positive about a stratified approach for choosing treatments but were wary of devolving clinical decisions to purely data-driven algorithms. These results reinforce the value of service user perspectives in the development and evaluation of novel treatment approaches

Ketamine treatment for depression : qualitative study exploring patient views

Background Ketamine is a new and promising treatment for depression but comes with challenges to implement because of its potential for abuse. Aims We sought the views of patients to inform policy and practical decisions about the clinical use of ketamine before large-scale roll-out is considered. Method This qualitative study used three focus groups and three validation sessions from 14 patients with prior diagnoses of depression but no experience of ketamine treatment. Focus groups explored their views about clinical use of ketamine and the best way for ketamine to be administered and monitored. The qualitative data were analysed by three service-user researchers using thematic analysis. Results Five themes were generated: changing public perceptions, risks, monitoring, privacy and data protection, and practical aspects. Participants were conscious of the stigma attached to ketamine as a street drug and wanted better public education, and evidence on the safety of ketamine after long-term use. They felt that monitoring was required to provide evidence for ketamine's safe use and administration, but there were concerns about the misuse of this information. Practical aspects included discussions about treatment duration, administration and accessibility (for example who would receive it, under what criteria and how). Conclusions Patients are enthusiastic about ketamine treatment but need more information before national roll-out. The wider societal impact of ketamine treatment also needs to be considered and patients need to be part of any future roll-out to ensure its success

Comparing professional and consumer ratings of mental health apps : mixed methods study

Background: As the number of mental health apps has grown, increasing efforts have been focused on establishing quality tailored reviews. These reviews prioritize clinician and academic views rather than the views of those who use them, particularly those with lived experiences of mental health problems. Given that the COVID-19 pandemic has increased reliance on web-based and mobile mental health support, understanding the views of those with mental health conditions is of increasing importance. Objective: This study aimed to understand the opinions of people with mental health problems on mental health apps and how they differ from established ratings by professionals. Methods: A mixed methods study was conducted using a web-based survey administered between December 2020 and April 2021, assessing 11 mental health apps. We recruited individuals who had experienced mental health problems to download and use 3 apps for 3 days and complete a survey. The survey consisted of the One Mind PsyberGuide Consumer Review Questionnaire and 2 items from the Mobile App Rating Scale (star and recommendation ratings from 1 to 5). The consumer review questionnaire contained a series of open-ended questions, which were thematically analyzed and using a predefined protocol, converted into binary (positive or negative) ratings, and compared with app ratings by professionals and star ratings from app stores. Results: We found low agreement between the participants’ and professionals’ ratings. More than half of the app ratings showed disagreement between participants and professionals (198/372, 53.2%). Compared with participants, professionals gave the apps higher star ratings (3.58 vs 4.56) and were more likely to recommend the apps to others (3.44 vs 4.39). Participants’ star ratings were weakly positively correlated with app store ratings (r=0.32, P=.01). Thematic analysis found 11 themes, including issues of user experience, ease of use and interactivity, privacy concerns, customization, and integration with daily life. Participants particularly valued certain aspects of mental health apps, which appear to be overlooked by professional reviewers. These included functions such as the ability to track and measure mental health and providing general mental health education. The cost of apps was among the most important factors for participants. Although this is already considered by professionals, this information is not always easily accessible. Conclusions: As reviews on app stores and by professionals differ from those by people with lived experiences of mental health problems, these alone are not sufficient to provide people with mental health problems with the information they desire when choosing a mental health app. App rating measures must include the perspectives of mental health service users to ensure ratings represent their priorities. Additional work should be done to incorporate the features most important to mental health service users into mental health apps

Can visual illustrations transform the patient information sheet for PET/MR neuroimaging studies into an engaging and interesting reading?

Every research study with human participants requires a participant information sheet (PIS). This is an important document that aims to provide to the study participants, a full description of the study and all procedures, individual risks, and research benefits. But besides its informative use, the PIS also provides the legal basis for an individual to consent to participate and must be agreed and signed prior to participation

How to make study documents clear and relevant : the impact of patient involvement

Background Patient and public involvement can improve study outcomes, but little data have been collected on why this might be. We investigated the impact of the Feasibility and Support to Timely Recruitment for Research (FAST-R) service, made up of trained patients and carers who review research documents at the beginning of the research pipeline. Aims To investigate the impact of the FAST-R service, and to provide researchers with guidelines to improve study documents. Method A mixed-methods design assessing changes and suggestions in documents submitted to the FAST-R service from 2011 to 2020. Quantitative measures were readability, word count, jargon words before and after review, the effects over time and if changes were implemented. We also asked eight reviewers to blindly select a pre- or post-review participant information sheet as their preferred version. Reviewers’ comments were analysed qualitatively via thematic analysis. Results After review, documents were longer and contained less jargon, but did not improve readability. Jargon and the number of suggested changes increased over time. Participant information sheets had the most suggested changes. Reviewers wanted clarity, better presentation and felt that documents lacked key information such as remuneration, risks involved and data management. Six out of eight reviewers preferred the post-review participant information sheet. FAST-R reviewers provided jargon words and phrases with alternatives for researchers to use. Conclusions Longer documents are acceptable if they are clear, with jargon explained or substituted. The highlighted barriers to true informed consent are not decreasing, although this study has suggestions for improving research document accessibility

Identifying schizophrenia stigma on Twitter : a proof of principle model using service user supervised machine learning

Stigma has negative effects on people with mental health problems by making them less likely to seek help. We develop a proof of principle service user supervised machine learning pipeline to identify stigmatising tweets reliably and understand the prevalence of public schizophrenia stigma on Twitter. A service user group advised on the machine learning model evaluation metric (fewest false negatives) and features for machine learning. We collected 13,313 public tweets on schizophrenia between January and May 2018. Two service user researchers manually identified stigma in 746 English tweets; 80% were used to train eight models, and 20% for testing. The two models with fewest false negatives were compared in two service user validation exercises, and the best model used to classify all extracted public English tweets. Tweets classed as stigmatising by service users were more negative in sentiment (t (744) = 12.02, p < 0.001 [95% CI: 0.196–0.273]). Our linear Support Vector Machine was the best performing model with fewest false negatives and higher service user validation. This model identified public stigma in 47% of English tweets (n5,676) which were more negative in sentiment (t (12,143) = 64.38, p < 0.001 [95% CI: 0.29–0.31]). Machine learning can identify stigmatising tweets at large scale, with service user involvement. Given the prevalence of stigma, there is an urgent need for education and online campaigns to reduce it. Machine learning can provide a real time metric on their success

Damage to the salience network and interactions with the default mode network

Interactions between the Salience Network (SN) and the Default Mode Network (DMN) are thought to be important for cognitive control. However, evidence for a causal relationship between the networks is limited. Previously, we have reported that traumatic damage to white matter tracts within the SN predicts abnormal DMN function. Here we investigate the effect of this damage on network interactions that accompany changing motor control. We initially used fMRI of the Stop Signal Task to study response inhibition in humans. In healthy subjects, functional connectivity (FC) between the right anterior insula (rAI), a key node of the SN, and the DMN transiently increased during stopping. This change in FC was not seen in a group of traumatic brain injury (TBI) patients with impaired cognitive control. Furthermore, the amount of SN tract damage negatively correlated with FC between the networks. We confirmed these findings in a second group of TBI patients. Here, switching rather than inhibiting a motor response: (1) was accompanied by a similar increase in network FC in healthy controls; (2) was not seen in TBI patients; and (3) tract damage after TBI again correlated with FC breakdown. This shows that coupling between the rAI and DMN increases with cognitive control and that damage within the SN impairs this dynamic network interaction. This work provides compelling evidence for a model of cognitive control where the SN is involved in the attentional capture of salient external stimuli and signals the DMN to reduce its activity when attention is externally focused

Terms and conditions apply : critical issues for readability and jargon in mental health depression apps

Background Mental health services are turning to technology to ease the resource burden, but privacy policies are hard to understand potentially compromising consent for people with mental health problems. The FDA recommends a reading grade of 8. Objective To investigate and improve the accessibility and acceptability of mental health depression app privacy policies. Methods A mixed methods study using quantitative and qualitative data to improve the accessibility of app privacy policies. Service users completed assessments and focus groups to provide information on ways to improve privacy policy accessibility, including identifying and rewording jargon. This was supplemented by comparisons of mental health depression apps with social media, music and finance apps using readability analyses and examining whether GDPR affected accessibility. Results Service users provided a detailed framework for increasing accessibility that emphasised having critical information for consent. Quantitatively, most app privacy policies were too long and complicated for ensuring informed consent (mental health apps mean reading grade = 13.1 (SD = 2.44)). Their reading grades were no different to those for other services. Only 3 mental health apps had a grade 8 or less and 99% contained service user identified jargon. Mental health app privacy policies produced for GDPR weren't more readable and were longer. Conclusions Apps specifically aimed at people with mental health difficulties are not accessible and even those that fulfilled the FDA's recommendation for reading grade contained jargon words. Developers and designers can increase accessibility by following a few rules and should, before launching, check whether the privacy policy can be understood