The meso-connectomes of mouse, marmoset, and macaque: network organization and the emergence of higher cognition.

The recent publications of the inter-areal connectomes for mouse, marmoset, and macaque cortex have allowed deeper comparisons across rodent vs. primate cortical organization. In general, these show that the mouse has very widespread, "all-to-all" inter-areal connectivity (i.e. a "highly dense" connectome in a graph theoretical framework), while primates have a more modular organization. In this review, we highlight the relevance of these differences to function, including the example of primary visual cortex (V1) which, in the mouse, is interconnected with all other areas, therefore including other primary sensory and frontal areas. We argue that this dense inter-areal connectivity benefits multimodal associations, at the cost of reduced functional segregation. Conversely, primates have expanded cortices with a modular connectivity structure, where V1 is almost exclusively interconnected with other visual cortices, themselves organized in relatively segregated streams, and hierarchically higher cortical areas such as prefrontal cortex provide top-down regulation for specifying precise information for working memory storage and manipulation. Increased complexity in cytoarchitecture, connectivity, dendritic spine density, and receptor expression additionally reveal a sharper hierarchical organization in primate cortex. Together, we argue that these primate specializations permit separable deconstruction and selective reconstruction of representations, which is essential to higher cognition.

Subgenual and Hippocampal Pathways in Amygdala Are Set to Balance Affect and Context Processing.

The amygdala, hippocampus, and subgenual cortex area 25 (A25) are engaged in complex cognitive-emotional processes. Yet pathway interactions from hippocampus and A25 with postsynaptic sites in amygdala remain largely unknown. In rhesus monkeys of both sexes, we studied with neural tracers how pathways from A25 and hippocampus interface with excitatory and inhibitory microcircuits in amygdala at multiple scales. We found that both hippocampus and A25 innervate distinct as well as overlapping sites of the basolateral (BL) amygdalar nucleus. Unique hippocampal pathways heavily innervated the intrinsic paralaminar basolateral nucleus, which is associated with plasticity. In contrast, orbital A25 preferentially innervated another intrinsic network, the intercalated masses, an inhibitory reticulum that gates amygdalar autonomic output and inhibits fear-related behaviors. Finally, using high-resolution confocal and electron microscopy (EM), we found that among inhibitory postsynaptic targets in BL, both hippocampal and A25 pathways preferentially formed synapses with calretinin (CR) neurons, which are known for disinhibition and may enhance excitatory drive in the amygdala. Among other inhibitory postsynaptic sites, A25 pathways innervated the powerful parvalbumin (PV) neurons which may flexibly regulate the gain of neuronal assemblies in the BL that affect the internal state. In contrast, hippocampal pathways innervated calbindin (CB) inhibitory neurons, which modulate specific excitatory inputs for processing context and learning correct associations. Common and unique patterns of innervation in amygdala by hippocampus and A25 have implications for how complex cognitive and emotional processes may be selectively disrupted in psychiatric disorders.SIGNIFICANCE STATEMENT The hippocampus, subgenual A25, and amygdala are associated with learning, memory, and emotions. We found that A25 is poised to affect diverse amygdalar processes, from emotional expression to fear learning by innervating the basal complex and the intrinsic intercalated masses. Hippocampal pathways uniquely interacted with another intrinsic amygdalar nucleus which is associated with plasticity, suggesting flexible processing of signals in context for learning. In the basolateral (BL) amygdala, which has a role in fear learning, both hippocampal and A25 interacted preferentially with disinhibitory neurons, suggesting a boost in excitation. The two pathways diverged in innervating other classes of inhibitory neurons, suggesting circuit specificities that could become perturbed in psychiatric diseases.

Untangling the association between COVID-19 health literacy, trust in the pandemic response, and mental distress, during the COVID-19 pandemic in Ireland: a repeated cross-sectional study.

BACKGROUND: The impact of the COVID-19 pandemic on rates of mental distress is well described. However, the contribution of poor health literacy and low levels of trust in state institutions to mental distress is less well defined. This study aimed to assess the impact of COVID-19 health literacy and trust in the pandemic response (Trust) on mental distress during the COVID-19 pandemic in Ireland. METHODS: We did this nationally representative cross-sectional survey of adult Irish residents during three study periods: from May 26 to June 17, 2020 (n=947); from July 1 to July 23, 2020 (n=995); and from Sept 5 to Sept 28, 2020 (n=972). Participants were contacted using random-digit-dialling and interviewed by a professional market research organisation (Ipsos MRBI' about 80% via mobile phone, 20% via landline). Mental distress was assessed by the Patient Health Questionnaire Anxiety Depression Scale (PHQ-ADS), for which a score of 10 or higher indicated mental distress. Heath literacy and trust were each assessed with three questions, which defined three categories: low, moderate, and high (appendix). Descriptive analysis and multivariate (MVA) Poisson regression were conducted in STATA17, Incidence Rate Ratios (IRR) are reported. FINDINGS: 2914 participants completed the survey across three study periods (median age 46 years, 1510 [51·8%] women, 1401 [48·1%] men, three [0·1%] non-binary). 804 (27·6%) of 2914 participants experienced mental distress (n=804). More women experienced mental distress than men (508 [34%] of women vs 294 [21%] of men). Mental distress was inversely associated with age (from 43% in those aged <30 years [n=232/539] to 19% in those aged >70 years [n=66/349]). Most participants had high health literacy (n=2,530, 86·8%). While health literacy was positively and significantly associated with trust, it was not associated with mental distress and it was therefore excluded from the MVA. Level of trust was captured for 2693 adults; 42·2% participants reported low trust (n=457) or moderate trust (n=679). The prevalence of mental distress was inversely associated with trust; increasing from 24% in those with high trust (n=374/1557), 30% in those with moderate trust (n=202/679), to 36% in those with low trust (n=166/457). In MVA higher rates of mental distress were associated with low trust (IRR 1·45, 95% CI 1·20-1·75; p=0·000) and moderate trust (IRR 1·24, 1·04-1·47, p=0·016) compared with high trust when adjusted for age, sex, employment status, and income,. INTERPRETATION: In Ireland, low levels of trust in the COVID-19 pandemic response were associated with higher levels of mental distress. Although poor health literacy was associated with low levels of trust, it was not independently associated with mental distress. Inference on the nature and direction of causal effects must be cautious given the cross-sectional study design. FUNDING: Health Research Board.

Disparities in the association between ambient temperature and preterm birth according to individual and regional characteristics: a nationwide time-stratified case-crossover study.

BACKGROUND: Several studies have reported that climate change elevates heat exposure in pregnant women and high temperatures during pregnancy are associated with preterm births (PTBs). Although the association might be disproportionate, related evidence remains sparse. We evaluated the disproportionate risk of PTB associated with ambient temperature during pregnancy by individual and regional characteristics in South Korea. METHODS: We collected data on birth certificates and daily mean temperatures during the period from 2011 to 2019. A time-stratified case-crossover design was used to investigate the association between temperature and PTB and stratified analyses were conducted to examine the effect modification of individual and regional characteristics. RESULTS: A total of 160,067 singleton PTBs were recorded in Korea from 2011 to 2019. A 5℃ increase in the mean temperature during the last four weeks before delivery was associated with an increased risk of PTB with an odds ratio (OR) of 1.03 (95% confidence interval [CI]: 1.02, 1.05), and the association was more evident in mothers aged ≥35 years (OR: 1.06 [95% CI: 1.03, 1.10]) and with low education levels (OR: 1.04 [95% CI: 1.02, 1.05]). Additionally, the estimated risk was evident in districts with lower medical resources and more prominent disparities were shown by individual and regional characteristics in rural areas than in urban areas. CONCLUSIONS: This study provides evidence that the risk of PTB related to ambient temperature is disproportionate by individual and regional characteristics and suggests the need for public health policies to alleviate the disparities, especially in rural areas.

Comparing times of self-harm presentations to hospital emergency departments in children, adolescents, young adults and adults: a national registry study 2007-2019.

PURPOSE: The few studies that have explored self-harm presentation times at hospital emergency departments (EDs) - an important factor that can determine if a patient receives a mental health assessment - primarily focus on adult samples. This study examined the times of self-harm presentations to EDs, self-harm methods used, mental health assessments, and admission data across different age-groups. METHODS: Using data from the National Self-Harm Registry Ireland over a 13-year timeframe (2007-2019), this study compared times, days, seasons, methods of self-harm, and admission data for children (8-12 years), adolescents (13-17 years), young adults (18-25 years) and adults (> 25 years). RESULTS: The majority of the 152,474 self-harm presentations (78.6%) for all ages occurred out-of-hours (outside the standard working hours or in-hours times of 09:00-17:00, Monday-Friday). The four hours before midnight had the highest proportions of self-harm presentations for adolescents (27.9%) and adults (23.1%), whereas the four hours after midnight had the highest proportion of self-harm presentations for young adults (22.9%). The 16:00-midnight timeframe had highest proportion of self-harm presentations in children (52.3%). Higher proportions of patients received a mental health assessment in-hours compared to out-of-hours among young adults (78.2% vs. 73.3%) and adults (76.1% vs. 72.0%). Self-harm presentations were lowest during summer months in children and adolescents. DISCUSSION: Hospitals should ensure that adequate resources are available for individuals presenting with self-harm, especially in the case of overcrowded EDs, and protocols need to be designed for those presenting with self-harm due to intoxication. In line with national policy, protocols for patients presenting during out-of-hours should be designed that can incorporate services from allied health multidisciplinary teams, social work, addiction services and counselling organisations. Given the lower rates of self-harm during school holidays for children and adolescents, the school environment must be considered in the context of mental health and self-harm public health prevention interventions.

Nanoscale imaging of pT217-tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: Evidence of interneuronal trafficking and early-stage neurodegeneration.

INTRODUCTION: Tau phosphorylated at threonine-217 (pT217-tau) is a novel fluid-based biomarker that predicts onset of Alzheimer's disease (AD) symptoms, but little is known about how pT217-tau arises in the brain, as soluble pT217-tau is dephosphorylated post mortem in humans. METHODS: We used multilabel immunofluorescence and immunoelectron microscopy to examine the subcellular localization of early-stage pT217-tau in entorhinal and prefrontal cortices of aged macaques with naturally occurring tau pathology and assayed pT217-tau levels in plasma. RESULTS: pT217-tau was aggregated on microtubules within dendrites exhibiting early signs of degeneration, including autophagic vacuoles. It was also seen trafficking between excitatory neurons within synapses on spines, where it was exposed to the extracellular space, and thus accessible to cerebrospinal fluid (CSF)/blood. Plasma pT217-tau levels increased across the age span and thus can serve as a biomarker in macaques. DISCUSSION: These data help to explain why pT217-tau predicts degeneration in AD and how it gains access to CSF and plasma to serve as a fluid biomarker.

Pathways for Memory, Cognition and Emotional Context: Hippocampal, Subgenual Area 25, and Amygdalar Axons Show Unique Interactions in the Primate Thalamic Reuniens Nucleus.

The reuniens nucleus (RE) is situated at the most ventral position of the midline thalamus. In rats and mice RE is distinguished by bidirectional connections with the hippocampus and medial prefrontal cortex (mPFC) and a role in memory and cognition. In primates, many foundational questions pertaining to RE remain unresolved. We addressed these issues by investigating the composition of the rhesus monkey RE in both sexes by labeling for GABA, a marker of inhibitory neurons, and for the calcium-binding proteins parvalbumin (PV), calbindin (CB), and calretinin (CR), which label thalamic excitatory neurons that project to cortex. As in rats and mice, the macaque RE was mostly populated by CB and CR neurons, characteristic of matrix-dominant nuclei, and had bidirectional connections with hippocampus and mPFC area 25 (A25). Unlike rodents, we found GABAergic neurons in the monkey RE and a sparser but consistent population of core-associated thalamocortical PV neurons. RE had stronger connections with the basal amygdalar complex than in rats or mice. Amygdalar terminations were enriched with mitochondria and frequently formed successive synapses with the same postsynaptic structures, suggesting an active and robust pathway to RE. Significantly, hippocampal pathways formed multisynaptic complexes that uniquely involved excitatory projection neurons and dendrites of local inhibitory neurons in RE, extending this synaptic principle beyond sensory to high-order thalamic nuclei. Convergent pathways from hippocampus, A25, and amygdala in RE position it to flexibly coordinate activity for memory, cognition, and emotional context, which are disrupted in several psychiatric and neurologic diseases in humans.SIGNIFICANCE STATEMENT The primate RE is a central node for memory and cognition through connections with the hippocampus and mPFC. As in rats or mice, the primate RE is a matrix-dominant thalamic nucleus, suggesting signal traffic to the upper cortical layers. Unlike rats or mice, the primate RE contains inhibitory neurons, synaptic specializations with the hippocampal pathway, and robust connections with the amygdala, suggesting unique adaptations. Convergence of hippocampal, mPFC, and amygdalar pathways in RE may help unravel a circuit basis for binding diverse signals for conscious flexible behaviors and the synthesis of memory with affective significance in primates, whereas disruption of distinct circuit nodes may occur in psychiatric disorders in humans.

Time of self-harm presentations to hospital emergency departments: a scoping review.

BACKGROUND: The time at which a self-harm presentation occurs has been shown to be a significant factor as to whether a patient receives a psychiatric assessment or not, which may benefit the patient's future care. This scoping review sought to identify studies that report on the peak time of day for self-harm presentations to hospital Emergency Departments (EDs). This could help hospital managers to properly allocate the appropriate services for self-harm patients when they are needed the most. METHODS: A scoping review of the literature from the year 2000 until 30th June 2021 was carried out using the PubMed, Web of Science, Embase and the Cochrane library databases. RESULTS: There were 22 studies that were included for data extraction. The findings from 20 of these studies indicate that self-harm presentations tend to occur outside of working hours (09:00-17:00, Monday to Friday). The majority of studies found that the peak time for self-harm presentations was in the hours before and after midnight. CONCLUSIONS: While this scoping review identified a satisfactory number of studies for data extraction, examination of time of day of presentation was a secondary outcome across most studies. Given that the majority of studies focused on adult samples, further research is necessary to investigate peak times for other age cohorts. More research on this topic is also needed in low- and middle-income countries. Consideration should be given to ensure that the necessary resources to treat hospital presenting self-harm are allocated outside of typical working hours.

Serial Prefrontal Pathways Are Positioned to Balance Cognition and Emotion in Primates.

The delicate balance among primate prefrontal networks is necessary for homeostasis and behavioral flexibility. Dorsolateral prefrontal cortex (dlPFC) is associated with cognition, while the most ventromedial subgenual cingulate area 25 (A25) is associated with emotion and emotional expression. Yet A25 is weakly connected with dlPFC, and it is unknown how the two regions communicate. In rhesus monkeys of both sexes, we investigated how these functionally distinct areas may interact through pregenual anterior cingulate area 32 (A32), which is strongly connected with both. We found that dlPFC innervated the deep layers of A32, while A32 innervated all layers of A25, mostly targeting spines of excitatory neurons. Approximately 20% of A32 terminations formed synapses on inhibitory neurons in A25, notably the powerful parvalbumin inhibitory neurons in the deep layers, and the disinhibitory calretinin neurons in the superficial layers. By innervating distinct inhibitory microenvironments in laminar compartments, A32 is positioned to tune activity in columns of A25. The circuitry of the sequential pathway indicates that when dlPFC is engaged, A32 can dampen A25 output through the parvalbumin inhibitory microsystem in the deep layers of A25. A32 thus may flexibly recruit or reduce activity in A25 to maintain emotional equilibrium, a process that is disrupted in depression. Moreover, pyramidal neurons in A25 had a heightened density of NMDARs, which are the targets of novel rapid-acting antidepressants. Pharmacologic antagonism of NMDARs in patients with depression may reduce excitability in A25, mimicking the effects of the neurotypical serial pathway identified here.SIGNIFICANCE STATEMENT The anterior cingulate is a critical hub in prefrontal networks through connections with functionally distinct areas. Dorsolateral and polar prefrontal areas that are associated with complex cognition are connected with the anterior cingulate in a pattern that allows them to indirectly control downstream activity from the anterior cingulate to the subgenual cingulate, which is associated with heightened activity and negative affect in depression. This set of pathways provides a circuit mechanism for emotional regulation, with the anterior cingulate playing a balancing role for integration of cognitive and emotional processes. Disruption of these pathways may perturb network function and the ability to regulate cognitive and affective processes based on context.

Evaluating the national multisite implementation of dialectical behaviour therapy in a community setting: a mixed methods approach.

BACKGROUND: The implementation of evidence-based interventions for borderline personality disorder in community settings is important given that individuals with this diagnosis are often extensive users of both inpatient and outpatient mental health services. Although work in this area is limited, previous studies have identified facilitators and barriers to successful DBT implementation. This study seeks to expand on previous work by evaluating a coordinated implementation of DBT in community settings at a national level. The Consolidated Framework for Implementation Research (CFIR) (Damschroder et al., Implementation Sci. 4:50, 2009) provided structural guidance for this national level coordinated implementation. METHODS: A mixed methods approach was utilised to explore the national multisite implementation of DBT from the perspective of team leaders and therapists who participated in the coordinated training and subsequent implementation of DBT. Qualitative interviews with DBT team leaders (n = 8) explored their experiences of implementing DBT in their local service and was analysed using content analysis. Quantitative surveys from DBT therapists (n = 74) examined their experience of multiple aspects of the implementation process including orienting the system, and preparations and support for implementation. Frequencies of responses were calculated. Written qualitative feedback was analysed using content analysis. RESULTS: Five themes were identified from the interview data: team formation, implementation preparation, client selection, service level challenges and team leader role. Participants identified team size and support for the team leader as key points for consideration in DBT implementation. Key challenges encountered were the lack of system support to facilitate phone coaching and a lack of allocated time to focus on DBT. Implementation facilitators included having dedicated team members and support from management. CONCLUSIONS: The barriers and facilitators identified in this study are broadly similar to those reported in previous research. Barriers and facilitators were identified across several domains of the CFIR and are consistent with a recently published DBT implementation Framework (Toms et al., Borderline Personal Disord Emot Dysregul. 6: 2, 2019). Future research should pay particular attention to the domain of characteristics of individuals involved in DBT implementation. The results highlight the importance of a mandated service plan for the coordinated implementation of an evidence-based treatment in a public health service. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03180541; Registered June 7th 2017 'retrospectively registered'.

Cortical Connections Position Primate Area 25 as a Keystone for Interoception, Emotion, and Memory.

The structural and functional integrity of subgenual cingulate area 25 (A25) is crucial for emotional expression and equilibrium. A25 has a key role in affective networks, and its disruption has been linked to mood disorders, but its cortical connections have yet to be systematically or fully studied. Using neural tracers in rhesus monkeys, we found that A25 was densely connected with other ventromedial and posterior orbitofrontal areas associated with emotions and homeostasis. A moderate pathway linked A25 with frontopolar area 10, an area associated with complex cognition, which may regulate emotions and dampen negative affect. Beyond the frontal lobe, A25 was connected with auditory association areas and memory-related medial temporal cortices, and with the interoceptive-related anterior insula. A25 mostly targeted the superficial cortical layers of other areas, where broadly dispersed terminations comingled with modulatory inhibitory or disinhibitory microsystems, suggesting a dominant excitatory effect. The architecture and connections suggest that A25 is the consummate feedback system in the PFC. Conversely, in the entorhinal cortex, A25 pathways terminated in the middle-deep layers amid a strong local inhibitory microenvironment, suggesting gating of hippocampal output to other cortices and memory storage. The graded cortical architecture and associated laminar patterns of connections suggest how areas, layers, and functionally distinct classes of inhibitory neurons can be recruited dynamically to meet task demands. The complement of cortical connections of A25 with areas associated with memory, emotion, and somatic homeostasis provide the circuit basis to understand its vulnerability in psychiatric and neurologic disorders.SIGNIFICANCE STATEMENT Integrity of the prefrontal subgenual cingulate cortex is crucial for healthy emotional function. Subgenual area 25 (A25) is mostly linked with other prefrontal areas associated with emotion in a dense network positioned to recruit large fields of cortex. In healthy states, A25 is associated with internal states, autonomic function, and transient negative affect. Constant hyperactivity in A25 is a biomarker for depression in humans and may trigger extensive activation in its dominant connections with areas associated with emotions and internal balance. A pathway between A25 and frontopolar area 10 may provide a critical link to regulate emotions and dampen persistent negative affect, which may be explored for therapeutic intervention in depression.

11 C-Metomidate PET/CT is a useful adjunct for lateralization of primary aldosteronism in routine clinical practice.

OBJECTIVE: To describe clinical practice experience of 11 C-Metomidate PET/CT as an adjunct to adrenal vein sampling (AVS) in the lateralization of aldosterone-producing adenomas (APA) in primary aldosteronism (PA). CONTEXT: Accurate lateralization of APA in the setting of PA offers the potential for surgical cure and improved long-term cardiovascular outcomes. Challenges associated with AVS, the current gold standard lateralization modality, mean that only a small proportion of potentially eligible patients currently make it through to surgery. This has prompted consideration of alternative strategies for lateralization, including the application of novel molecular PET tracers such as 11 C-Metomidate. DESIGN: Clinical Service Evaluation/Retrospective audit. PATIENTS: Fifteen individuals with a confirmed diagnosis of PA, undergoing lateralization with 11 C-Metomidate PET/CT prior to final clinical decision on surgical vs medical management. MEASUREMENTS: All patients underwent screening aldosterone renin ratio (ARR), followed by confirmatory testing with the seated saline infusion test, according to Endocrine Society Clinical Practice Guidelines. Adrenal glands were imaged using dedicated adrenal CT. 11 C-Metomidate PET/CT was undertaken due to equivocal or failed AVS. Management outcomes were assessed by longitudinal measurement of blood pressure, ARR, number of hypertensive medications following adrenalectomy or institution of medical therapy. RESULTS: We describe the individual lateralization and clinical outcomes for 15 patients with PA. CONCLUSION: 11 C-Metomidate PET/CT in conjunction with adrenal CT and AVS provided useful information which aided clinical decision-making for PA within a multidisciplinary hypertension clinic.

Evaluation of a virtual reality enhanced bullying prevention curriculum pilot trial.

INTRODUCTION: Bullying is a widely prevalent public health and safety issue that can have serious long-term consequences for youth. Given the limited efficacy of traditional bullying prevention programs, a need exists for novel, theoretically informed, prevention programming. Construal Level Theory provides a useful framework. METHODS: This study evaluated a pseudo-randomized pilot trial of a virtual reality enhanced bullying prevention program among middle school students (N = 118) in the Midwest United States. Two models were proposed. The first predicts reductions in bullying behavior (traditional bullying, cyberbullying, relational aggression) at post-test, mediated by changes in empathy in the virtual reality condition compared to the control condition. The second predicts increases in school belonging and willingness to intervene as an active bystander at post-test, mediated by changes in empathy in the virtual reality condition compared to the control condition. RESULTS: The virtual reality condition yielded increased empathy from pre-to post-intervention compared to the control condition. Through the mediating role of empathy, changes in the desirable directions were also observed for traditional bullying, sense of school belonging, and willingness to intervene as an active bystander, but not for cyberbullying or relational aggression. CONCLUSIONS: The scope and practical limitations of the virtual reality trial prevented a larger scale and more rigorous evaluation; however, results justify an expanded examination of virtual reality as a youth violence prevention tool.

Dialectical behaviour therapy for adolescents: a comparison of 16-week and 24-week programmes delivered in a public community setting.

BACKGROUND: Dialectical behaviour therapy for adolescents (DBT-A) is an intervention with a growing evidence base for treating adolescents with emotional and behavioural dysregulation. Previous studies have reported on varying lengths of treatment, however, and optimal treatment duration has not yet been identified. While the treatment developers initially proposed a 16-week programme, they have more recently recommended an extension to 24 weeks. This study compares outcomes for adolescents and parent/guardians who participated in 16- and 24-week DBT-A programmes in a community setting. METHODS: Eighty-four adolescents and 100 parent/guardians participated in 16-week DBT-A, while 68 adolescents and 67 parent/guardians participated in the 24-week programme. Outcome measures for adolescents included the presence and frequency of self-harm, suicidal ideation and depression; and for parents were burden, grief and parental stress. Outcomes were assessed at pre- and postintervention. Linear mixed-effects models were used to estimate the treatment duration effect (24-week vs. 16-week) utilising all available data at pre- and postintervention. RESULTS: Data analyses showed a reduction in the presence and frequency of self-harm at postintervention for adolescents in both programmes. Both adolescent and parent participants in the 16- and 24-week programmes also showed changes indicating significant improvement on all self-report outcome measures (p < .05). A treatment duration effect was identified with adolescents in the 24-week programme reporting greater gains on measures of suicidal ideation and depression (p < .05). However, drop-out rates were higher for the 24-week programme. CONCLUSIONS: The findings of the current study indicate that 24-week DBT-A may have additional benefits in comparison to 16-week DBT-A in terms of further reductions in suicidal ideation and depression. Given the nature of this study, it was not possible to explore a potential time effect, however, so these results should be interpreted with caution. Further research will assist in determining an optimal programme duration of DBT-A.

Innovations in Practice: Dialectical behaviour therapy for adolescents: multisite implementation and evaluation of a 16-week programme in a public community mental health setting.

BACKGROUND: Dialectical behaviour therapy for adolescents (DBT-A) is an intervention with a growing evidence base for treating adolescents with emotional and behavioural dysregulation. This study describes the implementation and effectiveness of 16-week DBT-A across multiple sites in publicly funded child/adolescent mental health services (CAMHS) in Ireland. METHOD: The Consolidated Framework for Implementation Research was used to guide this national implementation. Fifty-four clinicians from seven CAMHS teams completed DBT training and delivered the 16-week DBT-A programme. Eighty-four adolescents with emotional and behavioural dysregulation participated in the intervention and outcome measures were administered at preintervention, postintervention and 16-week follow-up. RESULTS: Significant reductions on all outcome measures were observed for DBT-A participants including presence and frequency of self-harm, suicidal ideation and depression. Reductions in the number of acute inpatient admissions, bed days and emergency department visits were also reported. CONCLUSIONS: DBT-A can be successfully implemented in CAMHS settings and yield positive outcomes for adolescents with emotional and behavioural dysregulation.

Pathway mechanism for excitatory and inhibitory control in working memory.

Humans engage in many daily activities that rely on working memory, the ability to hold and sequence information temporarily to accomplish a task. We focus on the process of working memory, based on circuit mechanisms for attending to relevant signals and suppressing irrelevant stimuli. We discuss that connections critically depend on the systematic variation in laminar structure across all cortical systems. Laminar structure is used to group areas into types regardless of their placement in the cortex, ranging from low-type agranular areas that lack layer IV to high-type areas that have six well-delineated layers. Connections vary in laminar distribution and strength based on the difference in type between linked areas, according to the "structural model" (Barbas H, Rempel-Clower N. Cereb Cortex 7: 635-646, 1997). The many possible pathways thus vary systematically by laminar distribution and strength, and they interface with excitatory neurons to select relevant stimuli and with functionally distinct inhibitory neurons that suppress activity at the site of termination. Using prefrontal pathways, we discuss how systematic architectonic variation gives rise to diverse pathways that can be recruited, along with amygdalar and hippocampal pathways that provide sensory, affective, and contextual information. The prefrontal cortex is also connected with thalamic nuclei that receive the output of the basal ganglia and cerebellum, which may facilitate fast sequencing of information. The complement of connections and their interface with distinct inhibitory neurons allows dynamic recruitment of areas and shifts in cortical rhythms to meet rapidly changing demands of sequential components of working memory tasks.

Dialectical behaviour therapy for treating adults and adolescents with emotional and behavioural dysregulation: study protocol of a coordinated implementation in a publicly funded health service.

BACKGROUND: In the Republic of Ireland, borderline personality disorder (BPD) is a feature of approximately 11-20% of clinical presentations to outpatient clinics within mental health services. These estimates are similar to other countries including the UK and USA. Dialectical behaviour therapy (DBT) is an intervention with a growing body of evidence that demonstrates its efficacy in treating individuals diagnosed with BPD. While a number of randomised controlled trials (RCTs) have demonstrated the efficacy of DBT, there is limited research which evaluates the effectiveness of this model when applied to real world settings. Funding was secured to co-ordinate DBT training in public community-based mental health services across Ireland. As no other study has evaluated a co-ordinated national implementation of DBT, the current study proposes to investigate the effectiveness of DBT in both adult and child/adolescent community mental health services across Ireland, evaluate the coordinated implementation of DBT at a national level, and complete a comprehensive economic evaluation comparing DBT versus treatment-as-usual. METHODS/ DESIGN: This study takes the form of a quasi-experimental design. Individuals attending community mental health services who meet criteria for participation in the DBT programme will be allocated to the intervention group. Individuals who live in areas in Ireland where DBT is not yet available, and individuals who choose not to participate in the intervention, will be invited to participate in a treatment-as-usual comparison group. Self-report clinical measures and health service use questionnaires for DBT participants (and parent/guardians as appropriate) will be administered at pre-, mid- and post-intervention, as well as follow-up for participants who complete the intervention. Survey and interview data for DBT therapists will be gathered at three time points: prior to DBT training, 6 months after teams begin delivery of the intervention, and 2 years following training completion. DISCUSSION: It is anticipated that the results of this study will provide evidence for the effectiveness of DBT for patients, and report on recommendations regarding best practice guidelines for implementation of DBT and its economic merit in a publicly funded service. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03180541 ; Registered June 7th 2017 'retrospectively registered'.

Correction to: Dialectical behaviour therapy for treating adults and adolescents with emotional and behavioural dysregulation: study protocol of a coordinated implementation in a publicly funded health service.

Upon publication of the original article (1) it was highlighted by the authors that there was just one error in the manuscript in the 'Sample size' subsection of the Methods/Design.

Innovations in Practice: Dialectical behaviour therapy - skills training for emotional problem solving for adolescents (DBT STEPS-A): evaluation of a pilot implementation in Irish post-primary schools.

BACKGROUND: Whole school approaches to mental health are recommended where schools and community partners work together to support positive mental health for young people. Universal interventions which adopt this approach are limited however. This study evaluates the pilot implementation of DBT STEPS-A, a social-emotional learning programme for adolescents, in Ireland. METHOD: Data were collected at the beginning and end of the academic year from students who participated in DBT STEPS-A and a control group. A matched comparison was conducted where a subset of the data was analysed consisting of 72 adolescents aged 15-16 years from two schools in the south of Ireland. Outcomes included emotion symptoms, dysfunctional coping and DBT skill use. Linear mixed-effects models were used to estimate the treatment effect (intervention vs. control). RESULTS: A statistically significant treatment effect was observed on two of four outcome measures (emotion symptom index: p = 0.011; internalising problems: p = 0.012). The effect sizes were large (Cohen's F squared = 0.65 and 0.83 respectively). CONCLUSIONS: Significant reductions on measures which assess constructs including depression, anxiety and social stress were found for the intervention group. The results suggest that DBT STEPS-A may yield positive effects for adolescents who complete the intervention. Feedback from adolescents and teachers suggests that refinement of content, structure and implementation may make the programme more accessible to an adolescent population.

Mirror trends of plasticity and stability indicators in primate prefrontal cortex.

Research on plasticity markers in the cerebral cortex has largely focused on their timing of expression and role in shaping circuits during critical and normal periods. By contrast, little attention has been focused on the spatial dimension of plasticity-stability across cortical areas. The rationale for this analysis is based on the systematic variation in cortical structure that parallels functional specialization and raises the possibility of varying levels of plasticity. Here, we investigated in adult rhesus monkeys the expression of markers related to synaptic plasticity or stability in prefrontal limbic and eulaminate areas that vary in laminar structure. Our findings revealed that limbic areas are impoverished in three markers of stability: intracortical myelin, the lectin Wisteria floribunda agglutinin, which labels perineuronal nets, and parvalbumin, which is expressed in a class of strong inhibitory neurons. By contrast, prefrontal limbic areas were enriched in the enzyme calcium/calmodulin-dependent protein kinase II (CaMKII), known to enhance plasticity. Eulaminate areas have more elaborate laminar architecture than limbic areas and showed the opposite trend: they were enriched in markers of stability and had lower expression of the plasticity-related marker CaMKII. The expression of glial fibrillary acidic protein (GFAP), a marker of activated astrocytes, was also higher in limbic areas, suggesting that cellular stress correlates with the rate of circuit reshaping. Elevated markers of plasticity may endow limbic areas with flexibility necessary for learning and memory within an affective context, but may also render them vulnerable to abnormal structural changes, as seen in neurologic and psychiatric diseases.