Engaging diverse patients in a diverse world: the development and preliminary evaluation of educational modules to support diversity in patient engagement research.

BACKGROUND: Current practices for engaging patients in patient-oriented research (POR) result in a narrow pool of patient perspectives being reflected in POR. This project aims to address gaps in methodological knowledge to foster diversity in POR, through the co-design and evaluation of a series of educational modules for health researchers in British Columbia, Canada. METHODS: Modules were co-created by a team of academic researchers and patient partners from hardly-reached communities. The modules are presented using the Tapestry Tool, an interactive, online educational platform. Our evaluation framework focused on engagement, content quality, and predicted behavior change. The User Engagement Scale short form (UES-SF) measured participants' level of engagement with the modules. Survey evaluation items assessed the content within the modules and participants' perceptions of how the modules will impact their behavior. Evaluation items modeled on the theory of planned behavior, administered before and after viewing the modules, assessed the impact of the modules on participants' perceptions of diversity in POR. RESULTS: Seventy-four health researchers evaluated the modules. Researchers' engagement and ratings of module content were high. Subjective behavioral control over fostering diversity in POR increased significantly after viewing the modules. CONCLUSIONS: Our results suggest the modules may be an engaging way to provide health researchers with tools and knowledge to increase diversity in health research. Future studies are needed to investigate best practices for engaging with communities not represented in this pilot project, such as children and youth, Indigenous Peoples, and Black communities. While educational interventions represent one route to increasing diversity in POR, individual efforts must occur in tandem with high-level changes that address systemic barriers to engagement.

Patient-Oriented research (POR) recognizes patients as partners in the research process, contributing valuable knowledge and lived experience to improve health outcomes and research translation. Unfortunately, POR presently does not represent all patients: patient partners involved in research tend to be white, middle-class women. Limited diversity in POR may limit research impact, in part because health research is not fully inclusive of the people requiring healthcare services and support. Although they recognize the need for diversity, many health researchers do not understand how to foster this. To empower health researchers with tools and knowledge to foster diversity in POR, we coordinated teams that co-created a set of educational modules. These teams included academic researchers and patient partners from seldom-heard communities in health research. The modules were built using the Tapestry Tool, an interactive, educational platform. We evaluated the modules using online surveys of 74 health researchers for three things: quality of module content, how engaging they were, and how they impacted health researchers' views on diversity in POR. Our results show that the modules' content was high quality and engaging. After viewing the modules, health researchers were more likely to feel like they had a role in engaging with more diverse people in their research, and felt that they had the tools, knowledge, and ability to do so. Education and knowledge for health researchers are a first step to increasing diversity in POR settings, but systemic barriers to inclusion also need attention.

Supporting Self-management and Quality of Life in Bipolar Disorder With the PolarUs App (Alpha): Protocol for a Mixed Methods Study.

BACKGROUND: Quality of life (QoL) is increasingly being recognized as a key outcome of interventions for bipolar disorder (BD). Mobile phone apps can increase access to evidence-based self-management strategies and provide real-time support. However, although individuals with lived experiences desire support with monitoring and improving broader health domains, existing BD apps largely target mood symptoms only. Further, evidence from the broader mobile health (mHealth) literature has shown that the desires and goals of end users are not adequately considered during app development, and as a result, engagement with mental health apps is suboptimal. To capitalize on the potential of apps to optimize wellness in BD, there is a need for interventions developed in consultation with real-world users designed to support QoL self-monitoring and self-management. OBJECTIVE: This mixed methods pilot study was designed to evaluate the alpha version of the newly developed PolarUs app, developed to support QoL self-monitoring and self-management in people with BD. Co-designed using a community-based participatory research framework, the PolarUs app builds on the web-based adaptation of a BD-specific QoL self-assessment measure and integrates material from a web-based portal providing information on evidence-informed self-management strategies in BD. The primary objectives of this project were to evaluate PolarUs app feasibility (via behavioral use metrics), the impact of PolarUs (via the Brief Quality of Life in Bipolar Disorder scale, our primary outcome measure), and explore engagement with the PolarUs app (via quantitative and qualitative methods). METHODS: Participants will be residents of North America (N=150), aged >18 years, with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of BD type 1, BD type 2, or BD not otherwise specified as assessed by structured diagnostic interview. An embedded mixed methods research design will be adopted; qualitative interviews with a purposefully selected subsample (approximately, n=30) of participants will be conducted to explore in more depth feasibility, impact, and engagement with the PolarUs app over the 12-week study period. RESULTS: At the time of publication of this protocol, the development of the alpha version of the PolarUs app was complete. Participant enrollment has begun in June 2022. Data collection is expected to be completed by December 2022. CONCLUSIONS: Beyond contributing knowledge on the feasibility and impact of a novel app to support QoL and self-management in BD, this study will also provide new insights related to engagement with mHealth apps. Furthermore, it will function as a case study of successful co-design between people with BD, health care providers, and BD researchers, providing a template for the future use of community-based participatory research frameworks in mHealth intervention development. The results will be used to further refine the PolarUs app and inform the design of a larger clinical trial. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/36213.

Evaluating the quality, safety, and functionality of commonly used smartphone apps for bipolar disorder mood and sleep self-management.

BACKGROUND: Individuals with bipolar disorder (BD) are increasingly turning to smartphone applications (apps) for health information and self-management support. While reviews have raised concerns regarding the effectiveness and safety of publicly available apps for BD, apps surveyed may not reflect what individuals with BD are using. The present study had two aims: first, to characterize the use of health apps to support mood and sleep amongst people with BD, and second, to evaluate the quality, safety and functionality of the most commonly used self-management apps. METHODS: A web-based survey was conducted to explore which apps people with BD reported using to support self-management of mood and sleep. The characteristics of the most commonly nominated apps were described using a standardized framework, including their privacy policy, clinical foundations, and functionality. RESULTS: Respondents (n = 919) were 77.9% female with a mean age of 36.9 years. 41.6% of participants (n = 382) reported using a self-management app to support mood or sleep. 110 unique apps were nominated in relation to mood, and 104 unique apps nominated in relation to sleep; however, most apps were only mentioned once. The nine most frequently nominated apps related to mood and sleep were subject to further evaluation. All reviewed apps offered a privacy policy, however user control over data was limited and the complexity of privacy policies was high. Only one app was developed for BD populations. Half of reviewed apps had published peer-reviewed evidence to support their claims of efficacy, but little research was specific to BD. CONCLUSION: Findings illustrate the potential of smartphone apps to increase the reach of psychosocial interventions amongst people with BD. Apps were largely created by commercial developers and designed for the general population, highlighting a gap in the development and dissemination of evidence-informed apps for BD. There may be risks in using generic health apps for BD self-management; clinicians should enquire about patients' app use to foster conversations about their particular benefits and limitations.

Digital Health Literacy in Bipolar Disorder: International Web-Based Survey.

BACKGROUND: Web-based resources can support people with bipolar disorder (BD) to improve their knowledge and self-management. However, publicly available resources are heterogeneous in terms of their quality and ease of use. Characterizing digital health literacy (the skillset that enable people to navigate and make use of health information in a web-based context) in BD will support the development of educational resources. OBJECTIVE: The aim of this study was to develop understanding of digital health literacy and its predictors in people with BD. METHODS: A web-based survey was used to explore self-reported digital health literacy (as measured by the e-Health Literacy Scale [eHEALS]) in people with BD. Multiple regression analysis was used to evaluate potential predictors, including demographic/clinical characteristics and technology use. RESULTS: A total of 919 respondents (77.9% female; mean age 36.9 years) completed the survey. Older age (ß=0.09; P=.01), postgraduate education (ß=0.11; P=.01), and current use of self-management apps related to BD (ß=0.13; P<.001) were associated with higher eHEALS ratings. CONCLUSIONS: Levels of self-reported digital health literacy were comparable or higher than other studies in the general population and specific physical/mental health conditions. However, individuals with BD who are younger, have completed less education, or are less familiar with mental health apps may require extra support to safely and productively navigate web-based health resources. Relevant educational initiatives are discussed. Future studies should evaluate skill development interventions for less digitally literate groups.

Use of smartphone apps in bipolar disorder: An international web-based survey of feature preferences and privacy concerns.

BACKGROUND: Smartphone apps have potential for delivering interventions and supporting self-management in bipolar disorder (BD), however clinical trials of mental health apps have high dropout rates and low sustained use in real-world contexts. To support the development of app-based interventions, we explored use of and attitudes towards apps amongst people with BD, specifically concerns about privacy and preferences for various app features. METHODS: An international web-based survey was used to investigate concerns about privacy and the perceived importance of various app features among people with BD. Quantitative findings were summarised using descriptive statistics. Qualitative content analysis was used to investigate free-text responses. RESULTS: A total of 919 people completed the survey; 97.5% reported using smartphone apps in general. Concerns regarding data security were prevalent. Commonly prioritised mHealth features included content quality/accuracy, ease and flexibility of use, cost, and data security. The ability to share data with others, rewards for use, inter-app connectivity, and peer support were endorsed as important by fewer than half of respondents. Qualitative findings suggested that sustained app use could be supported by novel and positive content, customisation, meaningful use of data, interactivity, and perceived real-world benefits. CONCLUSIONS: The findings of the present study offer important design considerations for the development and evaluation of future app-based interventions for BD. Importantly, some features that have previously been suggested as clinically beneficial or likely to support engagement were perceived ambivalently, emphasising the need for in-depth consultation with potential end users during app development.

Beyond clicks and downloads: a call for a more comprehensive approach to measuring mobile-health app engagement.

Downloading a mobile health (m-health) app on your smartphone does not mean you will ever use it. Telling another person about an app does not mean you like it. Using an online intervention does not mean it has had an impact on your well-being. Yet we consistently rely on downloads, clicks, 'likes' and other usage and popularity metrics to measure m-health app engagement. Doing so misses the complexity of how people perceive and use m-health apps in everyday life to manage mental health conditions. This article questions commonly used behavioural metrics of engagement in mental health research and care, and proposes a more comprehensive approach to measuring in-app engagement.

Supporting Self-Management in Bipolar Disorder: Mixed-Methods Knowledge Translation Study.

BACKGROUND: Self-management is increasingly recognized as an important method through which individuals with bipolar disorder (BD) may cope with symptoms and improve quality of life. Digital health technologies have strong potential as a method to support the application of evidence-informed self-management strategies in BD. Little is known, however, about how to most effectively maximize user engagement with digital platforms. OBJECTIVE: The aims of this study were (1) to create an innovative Web-based Bipolar Wellness Centre, (2) to conduct a mixed-methods (ie, quantitative and qualitative) evaluation to assess the impact of different sorts of engagement (ie, knowledge translation [KT]), and (3) to support engagement with the self-management information in the Bipolar Wellness Centre. METHODS: The project was implemented in 2 phases. In phase 1, community-based participatory research and user-centered design methods were used to develop a website (Bipolar Wellness Centre) housing evidence-informed tools and strategies for self-management of BD. In phase 2, a mixed-methods evaluation was conducted to explore the potential impact of 4 KT strategies (Web-based webinars, Web-based videos, Web-based one-to-one Living Library peer support, and in-person workshops). Quantitative assessments occurred at 2 time points-preintervention and 3 weeks postintervention. Purposive sampling was used to recruit a subsample of participants for the qualitative interviews, ensuring each KT modality was represented, and interviews occurred approximately 3 weeks postintervention. RESULTS: A total of 94 participants were included in the quantitative analysis. Responses to evaluative questions about engagement were broadly positive. When averaged across the 4 KT strategies, significant improvements were observed on the Bipolar Recovery Questionnaire (F1,77=5.887; P=.02) and Quality of Life in Bipolar Disorder (F1,77=8.212; P=.005). Nonsignificant improvements in positive affect and negative affect were also observed. The sole difference that emerged between KT strategies related to the Chronic Disease Self-Efficacy measure, which decreased after participation in the webinar and video arms but increased after the Living Library and workshop arms. A subsample of 43 participants was included in the qualitative analyses, with the majority of participants describing positive experiences with the 4 KT strategies; peer contact was emphasized as a benefit across all strategies. Infrequent negative experiences were reported in relation to the webinar and video strategies, and included technical difficulties, the academic tone of webinars, and feeling unable to relate to the actor in the videos. CONCLUSIONS: This study adds incremental evidence to a growing literature that suggests digital health technologies can provide effective support for self-management for people with BD. The finding that KT strategies could differentially impact chronic disease self-efficacy (hypothesized as being a product of differences in degree of peer contact) warrants further exploration. Implications of the findings for the development of evidence-informed apps for BD are discussed in this paper.

Online and mobile technologies for self-management in bipolar disorder: A systematic review.

OBJECTIVE: Internet (eHealth) and smartphone-based (mHealth) approaches to self-management for bipolar disorder are increasingly common. Evidence-based self-management strategies are available for bipolar disorder and provide a useful framework for reviewing existing eHealth/mHealth programs to determine whether these strategies are supported by current technologies. This review assesses which self-management strategies are most supported by technology. METHOD: Based on 3 previous studies, 7 categories of self-management strategies related to bipolar disorder were identified, followed by a systematic literature review to identify existing eHealth and mHealth programs for this disorder. Searches were conducted by using PubMed, CINAHL, PsycINFO, EMBASE, and the Cochrane Database of Systematic Reviews for relevant peer-reviewed articles published January 2005 to May 2015. eHealth and mHealth programs were summarized and reviewed to identify which of the 7 self-management strategy categories were supported by eHealth or mHealth programs. RESULTS: From 1,654 publications, 15 papers were identified for inclusion. From these, 9 eHealth programs and 2 mHealth programs were identified. The most commonly supported self-management strategy categories were "ongoing monitoring," "maintaining hope," "education," and "planning for and taking action"; the least commonly supported categories were "relaxation" and "maintaining a healthy lifestyle." eHealth programs appear to provide more comprehensive coverage of self-management strategies compared with mHealth programs. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Both eHealth and mHealth programs present a wide range of self-management strategies for bipolar disorder, although individuals seeking comprehensive interventions might be best served by eHealth programs, while those seeking more condensed and direct interventions might prefer mHealth programs. (PsycINFO Database Record

Bipolar disorder research 2.0: Web technologies for research capacity and knowledge translation.

RATIONALE, AIMS AND OBJECTIVES: Current Web technologies offer bipolar disorder (BD) researchers many untapped opportunities for conducting research and for promoting knowledge exchange. In the present paper, we document our experiences with a variety of Web 2.0 technologies in the context of an international BD research network: The Collaborative RESearch Team to Study psychosocial issues in BD (CREST.BD). METHODS: Three technologies were used as tools for enabling research within CREST.BD and for encouraging the dissemination of the results of our research: (1) the crestbd.ca website, (2) social networking tools (ie, Facebook, Twitter), and (3) several sorts of file sharing (ie YouTube, FileShare). For each Web technology, we collected quantitative assessments of their effectiveness (in reach, exposure, and engagement) over a 6-year timeframe (2010-2016). RESULTS: In general, many of our strategies were deemed successful for promoting knowledge exchange and other network goals. We discuss how we applied our Web analytics to inform adaptations and refinements of our Web 2.0 platforms to maximise knowledge exchange with people with BD, their supporters, and health care providers. CONCLUSIONS: We conclude with some general recommendations for other mental health researchers and research networks interested in pursuing Web 2.0 strategies.

Effective self-management strategies for bipolar disorder: A community-engaged Delphi Consensus Consultation study.

BACKGROUND: Self-management represents an important complement to psychosocial treatments for bipolar disorder (BD), but research is limited. Specifically, little is known about self-management approaches for elevated mood states; this study investigated self-management strategies for: (1) maintaining balance in mood, and (2) stopping progression into hypomania/mania. METHODS: To identify the common components of BD self-management, Delphi Consensus Consultation methods were combined with a Community-Based Participatory Research (CBPR) approach across five study phases: (1) Qualitative dataset content analysis; (2) Academic/grey literature reviews; (3) Content analysis; (4) Two Delphi rounds (rating strategies on a 5-point Likert scale, Very Unhelpful-Very Helpful), and; (5) Quantitative analysis and interpretation. Participants were people with BD and healthcare providers. RESULTS: Phases 1 and 2 identified 262 and 3940 candidate strategies, respectively; 3709 were discarded as duplicates/unintelligible. The remaining 493 were assessed via Delphi methods in Phase 4: 101 people with BD and 52 healthcare providers participated in Round 1; 83 of the BD panel (82%) and 43 of the healthcare provider panel (83%) participated in Round 2-exploratory factor analysis (EFA) was conducted on Round 2 results. LIMITATIONS: EFA was underpowered and sample was not ethnically diverse, limiting generalizability. DISCUSSION: High concordance was observed in ratings of strategy effectiveness between the two panels. Future research could usefully investigate the provisional discovery here of underlying factors which link individual strategies. For example, 'maintaining hope' underpinned strategies for maintaining balance, and 'decreasing use of stimulants' underpinned strategies to interrupt hypo/manic ascent. There is merit in combining CBPR and Delphi methods.

Harnessing the potential of community-based participatory research approaches in bipolar disorder.

BACKGROUND: Despite the rapid growth in the sophistication of research on bipolar disorder (BD), the field faces challenges in improving quality of life (QoL) and symptom outcomes, adapting treatments for marginalized communities, and disseminating research insights into real-world practice. Community-based participatory research (CBPR)-research that is conducted as a partnership between researchers and community members-has helped address similar gaps in other health conditions. This paper aims to improve awareness of the potential benefits of CBPR in BD research. METHODS: This paper is a product of the International Society for Bipolar Disorders (ISBD) Taskforce on Community Engagement which includes academic researchers, healthcare providers, people with lived experience of BD, and stakeholders from BD community agencies. Illustrative examples of CBPR in action are provided from two established centres that specialize in community engagement in BD research: the Collaborative RESearch Team to study psychosocial issues in BD (CREST.BD) in Canada, and the Spectrum Centre for Mental Health Research in the United Kingdom. RESULTS AND DISCUSSION: We describe the philosophy of CBPR and then introduce four core research areas the BD community has prioritized for research: new treatment approaches, more comprehensive outcome assessments, tackling stigma, and enhanced understanding of positive outcomes. We then describe ways in which CBPR is ideal for advancing each of these research areas and provide specific examples of ways that CBPR has already been successfully applied in these areas. We end by noting potential challenges and mitigation strategies in the application of CBPR in BD research. CONCLUSIONS: We believe that CBPR approaches have significant potential value for the BD research community. The observations and concerns of people with BD, their family members, and supports clearly represent a rich source of information. CBPR approaches provide a collaborative, equitable, empowering orientation to research that builds on the diversity of strengths amongst community stakeholders. Despite the potential merits of this approach, CBPR is as yet not widely used in the BD research field, representing a missed opportunity.

Creativity and Bipolar Disorder: Igniting a Dialogue.

Bipolar disorder (BD) has been related to heightened creativity, yet core questions remain unaddressed about this association. We used qualitative methods to investigate how highly creative individuals with BD understand the role of symptoms and treatment in their creativity, and possible mechanisms underpinning this link. Twenty-two individuals self-identified as highly creative and living with BD took part in focus groups and completed quantitative measures of symptoms, quality of life (QoL), and creativity. Using thematic analysis, five themes emerged: the pros and cons of mania for creativity, benefits of altered thinking, the relationship between creativity and medication, creativity as central to one's identity, and creativity's importance in stigma reduction and treatment. Despite reliance on a small sample who self-identified as having BD, findings shed light on previously mixed results regarding the influence of mania and treatment and suggest new directions for the study of mechanisms driving the creative advantage in BD.

Established non-union of an operatively managed trans-scaphoid perilunate fracture dislocation progressing to spontaneous union.

Perilunate dislocations and fracture dislocations represent uncommon and unusual injuries that are often missed at initial presentation and diagnosed late in up to 25% of cases. Prompt open reduction, carpal stabilisation and ligamentous repair is required to reduce the risk of complications. We report a case of an established scaphoid non-union in an operatively managed perilunate fracture dislocation that spontaneously united almost 2 years after the initial injury, just before a planned revision scaphoid fixation with bone grafting. This case highlights the importance of initial clinical assessment together with appropriate radiographs and follow-up of these injuries post-operatively, especially when complications such as non-union arise.

Stable mossy fiber long-term potentiation requires calcium influx at the granule cell soma, protein synthesis, and microtubule-dependent axonal transport.

The synapses formed by the mossy fiber (MF) axons of hippocampal dentate gyrus granule neurons onto CA3 pyramidal neurons exhibit an intriguing form of experience-dependent synaptic plasticity that is induced and expressed presynaptically. In contrast to most other CNS synapses, long-term potentiation (LTP) at the MF-CA3 synapse is readily induced even during blockade of postsynaptic glutamate receptors. Furthermore, blocking voltage-gated Ca(2+) channels prevents MF-LTP, supporting an involvement of presynaptic Ca(2+) signaling via voltage-gated Ca(2+) channels in MF-LTP induction. We examined the contribution of activity in both dentate granule cell somata and MF terminals to MF-LTP. We found that the induction of stable MF-LTP requires tetanization-induced action potentials not only at MF boutons, but also at dentate granule cell somata. Similarly, blocking Ca(2+) influx via voltage-gated Ca(2+) channels only at the granule cell soma was sufficient to disrupt MF-LTP. Finally, blocking protein synthesis or blocking fast axonal transport mechanisms via disruption of axonal tubulin filaments resulted in decremental MF-LTP. Collectively, these data suggest that-in addition to Ca(2+) influx at the MF terminals-induction of MF synaptic plasticity requires action potential-dependent Ca(2+) signaling at granule cell somata, protein synthesis, and fast axonal transport along MFs. A parsimonious interpretation of these results is that somatic activity triggers protein synthesis at the soma; newly synthesized proteins are then transported to MF terminals, where they contribute to the stabilization of MF-LTP. Finally, the present data imply that synaptic plasticity at the MF-CA3 synapse can be affected by local modulation of somatic and presynaptic Ca(2+) channel activity.

Association of study type, sample size, and follow-up length with type of recommendation produced by the National Institute for Health and Clinical Excellence Interventional Procedures Programme.

OBJECTIVES: The association between type and amount of clinical evidence and type of National Institute for Health and Clinical Excellence recommendations for interventional procedures was examined. METHODS: The evidence about 736 studies (including 183,729 patients) relating to 130 different interventional procedures and about relevant recommendations was analyzed. Associations were examined between type of recommendation ("normal arrangements" or "cautionary guidance") and evidence type, total number of treated patients, and mean follow-up length. Evidence type was categorized as (a) randomized, (b) nonrandomized controlled, and (c) case series/reports. The main outcome measures were frequency of evidence type, total number of patients treated, and mean follow-up length, by type of recommendation. RESULTS: "Normal arrangements" recommendations were made for 70 (54 percent) procedures and "cautionary guidance" was issued for 60 (46 percent) procedures. Procedures supported by at least one randomized study (34 percent, n = 44) were more likely to receive a "normal arrangements" recommendation (relative risk 1.38, p = .063). Overall, there were 85 (12 percent), 135 (18 percent), and 516 (70 percent) studies in categories a-c, respectively. The number of treated patients was significantly larger among procedures with "normal arrangements" (median, 605; range, 26-6,842) than among those with "cautionary guidance" (median, 240; range, 1-3,261; p < .001) recommendation. Mean follow-up length was longer in studies relating to procedures with "normal arrangements" recommendation (median, 16.7; range, 0-84 months) compared with those with "cautionary guidance" (median, 14.6; range, 0-67 months; p = .160). CONCLUSIONS: Procedures supported by randomized studies, and with larger numbers of patients and longer follow-up length, were more likely to receive positive guidance. Future research and development on interventional procedures should aim to produce better and more relevant evidence to optimize the possibility of such procedures being accepted by policy makers.

Kindling of basolateral amygdala but not ventral hippocampus or perirhinal cortex disrupts sensorimotor gating in rats.

The neural mechanisms mediating prepulse inhibition (PPI) appear to have relevance to neurological and psychiatric disorders. Patients with temporal lobe epilepsy exhibit psychotic symptoms and disrupted PPI, therefore the present experiments examined the consequences of seizures induced by kindling on PPI. Rats were chronically implanted with an electrode into the basolateral amygdala, perirhinal cortex, or ventral hippocampus and stimulated twice daily until 3 fully generalized, class 5 seizures were elicited. Kindling of basolateral amygdala, but not perirhinal cortex or ventral hippocampus, disrupted PPI when testing began 2min, but not 48h, following the elicitation of the third class 5 seizure. Startle amplitudes were unaffected by kindling. These results suggest that the anatomical origin of seizures is an important factor in determining their potentially disruptive effects on PPI.

Effects of expectation on amygdala-kindled convulsions and interictal behaviour in rats: confirmation of a Pavlovian mechanism.

We found evidence that the effects of exposure to the stimulation environment on the convulsions and interictal behaviour of basolateral amygdala (BA)-kindled rats are the result of Pavlovian conditioning. In Experiment 1, the rats first received 45 BA stimuli in one environment (CS+) and 45 sham stimuli in another environment (CS-). During this first phase of the experiment, the CS+ and CS- began to exert differential effects on interictal behaviour and convulsions. Then, during the second phase, rats received 45 stimuli and 45 sham stimuli, either as before in their original CS+ and CS- (nonreversal rats) or with their original CS+ and CS- interchanged (reversal rats). During the second phase, the CS+ and CS- continued to exert the same pattern of differential effects on the interictal behaviour and convulsions of the nonreversal rats, whereas the reversal rats began to display the reverse pattern. In Experiment 2, rats received 60 sham stimuli in one environment (CS1). Then, half of the rats received 30 stimuli in a second environment (CS2) and 30 sham stimuli in CS1 (no-pre-exposure rats), whereas the other half (pre-exposure rats) received 30 stimuli and 30 sham stimuli in CS1. Pre-exposure to the stimulation environment attenuated the kindled convulsions. These findings confirm that the conditioned effects of kindling are mediated by a Pavlovian mechanism.

Conditioned effects of kindling three different sites in the hippocampal complex of the rat.

Rats received kindling stimulations to the perirhinal cortex (PRh), ventral hippocampus (VH), or dorsal hippocampus (DH) in 1 environment and an equivalent number of sham stimulations in a 2nd environment. The PRh-kindled rats displayed rapid kindling and a swift emergence of conditioned interictal defensiveness. In contrast, the VH- and DH-kindled rats displayed much slower kindling and slow or no conditioning, respectively. No effects of conditioning on the convulsions, comparable with those associated with amygdala kindling, were observed. These results establish the generality of some of the previously reported kindling-related conditioned effects, confirm the site specificity of some of these effects, and suggest that the convulsions, rather than the stimulations, function as the unconditioned stimuli for the conditioning of interictal behavior.

Anticipating the attack: temporal conditioning during amygdala kindling in rats.

The present study showed that amygdala-kindled rats use short-interval timing superimposed on phase or ordinal timing to predict when a convulsion will occur. In 2 experiments, rats received 1 stimulation and 1 sham stimulation each day, always at the same times (conditioned stimulus [CS]+ and CS- times, respectively) and 150 s after rats had been placed in the testing chamber (the preadministration interval). As kindling progressed, the rats displayed more defensive behavior at the CS+ time than at the CS- time. Then, a stimulation-free peak-procedure test was conducted: At the CS+ time, but not at the CS- time, defensive behavior increased progressively as the 150-s preadministration interval elapsed, and then it gradually declined.