Ethics, design, and implementation criteria of digital assistive technologies for people with dementia from a multiple stakeholder perspective: a qualitative study.

BACKGROUND: Dementia impairs the ability of people with dementia to be autonomous and independent. They need support from third parties, who should ideally respect their autonomy and independence as much as possible. Supporting people with dementia can be very burdensome for caregivers and numbers of patients increase while numbers of potential caregivers decline. Digital assistive technologies (DATs) that directly support patients or their caregivers may help bridging the increasing gap between need of support and available resources. DATs have the potential to preserve the autonomy and independence of people with dementia and promote their abilities, if they are properly designed in close interaction with future users. In our study, we focused on ethical concerns, technological requirements, and implementation criteria for DAT in general and specifically to support outdoor mobility of people with dementia. METHODS: We applied a qualitative approach and conducted a World Café (2 tables, n = 7) and an online focus group (n = 6) with people with dementia, relatives, healthcare professionals, scientists, ethics experts, and experts for digitally-assisted medical care. We descriptively analyzed the data using a content analysis approach. RESULTS: The participants reported technological (e.g., lack of Wi-Fi), financial (e.g., expensive devices or lack of budget for DATs), political (e.g., legal hurdles such as the European Medical Device Law or data protection regulations) as well as user-related hurdles (e.g., lack of digital competence) for the implementation of DAT in dementia care. Among the issues discussed were the importance of autonomy, independence, safety, privacy, and questions of decision making capacity in DAT's use. Participants identified opportunities and benefits in self-learning, situation-aware DATs and wished for dementia-friendly communities. They emphasized the value of personal interaction that should not be replaced, but rather supported by DAT. CONCLUSION: The results revealed multiple hurdles and ethical concerns for DAT use and provided recommendations for designing and implementing DATs. Further investigations are needed on the impact of DAT on personal interactions in caregiving and the role of DAT in dementia-friendly communities.

Smartwatch-Based Interventions for People With Dementia: User-Centered Design Approach.

BACKGROUND: Assistive technologies can help people living with dementia maintain their everyday activities. Nevertheless, there is a gap between the potential and use of these materials. Involving future users may help close this gap, but the impact on people with dementia is unclear. OBJECTIVE: We aimed to determine if user-centered development of smartwatch-based interventions together with people with dementia is feasible. In addition, we evaluated the extent to which user feedback is plausible and therefore helpful for technological improvements. METHODS: We examined the interactions between smartwatches and people with dementia or people with mild cognitive impairment. All participants were prompted to complete 2 tasks (drinking water and a specific cognitive task). Prompts were triggered using a smartphone as a remote control and were repeated up to 3 times if participants failed to complete a task. Overall, 50% (20/40) of the participants received regular prompts, and 50% (20/40) received intensive audiovisual prompts to perform everyday tasks. Participants' reactions were observed remotely via cameras. User feedback was captured via questionnaires, which included topics like usability, design, usefulness, and concerns. The internal consistency of the subscales was calculated. Plausibility was also checked using qualitative approaches. RESULTS: Participants noted their preferences for particular functions and improvements. Patients struggled with rating using the Likert scale; therefore, we assisted them with completing the questionnaire. Usability (mean 78 out of 100, SD 15.22) and usefulness (mean 9 out of 12) were rated high. The smartwatch design was appealing to most participants (31/40, 76%). Only a few participants (6/40, 15%) were concerned about using the watch. Better usability was associated with better cognition. The observed success and self-rated task comprehension were in agreement for most participants (32/40, 80%). In different qualitative analyses, participants' responses were, in most cases, plausible. Only 8% (3/40) of the participants were completely unaware of their irregular task performance. CONCLUSIONS: People with dementia can have positive experiences with smartwatches. Most people with dementia provided valuable information. Developing assistive technologies together with people with dementia can help to prioritize the future development of functional and nonfunctional features.

Design and implementation of the participatory German network for translational dementia care research (TaNDem): A mixed-method study on the perspectives of healthcare providers and dementia researchers in dementia care research.

BACKGROUND: Currently, there is a lack of interaction between research and healthcare practice. As a result, research findings reach healthcare practice only late, and topics relevant to practice are often not known in research. Involving people living with dementia (PlwD), their relatives and healthcare providers in dementia care research can accelerate this process. For inclusion, firm and reliable structures are needed, which are to be established with the help of the Translational Network for Dementia Care Research in Germany. However, there is only limited knowledge about the priorities, expectations and conditions of stakeholders (healthcare providers and dementia researchers) for such cooperation within a network. OBJECTIVES: The aim is to gather stakeholders' views on (i) future research topics to be addressed within the dementia care research network, (ii) the nature of collaboration within the network and (iii) the facilitating and hindering factors for establishing such a network. METHODS: Within an exploratory sequential mixed-method study, we interviewed 87 stakeholders within eleven semistructured focus group interviews. The interviews were transcribed, pseudonymized and analyzed using qualitative content analysis. The qualitative data were analyzed with MAXQDA. Based on the qualitative results found in the focus group interviews, a supplementary online questionnaire was developed to prioritise and rank these findings afterwards. RESULTS: Stakeholders prioritized a comprehensible transfer of research results into practice, increased involvement of PlwD and their relatives (additionally marginalized groups such as people with a migrant background) in research and exchange between researchers. Cooperation should preferably occur in a regional context with local contacts, and the latest research results should be made available via an online database. The stakeholders' time, finances and human resources should be considered. CONCLUSION: Stakeholders have partly similar preferences and goals for cooperation and involvement, emphasizing that such interaction in a network offers the possibility of long-term, effective collaboration and added value for practice and research. PATIENT OR PUBLIC CONTRIBUTION: For this study, dementia healthcare providers and dementia care researchers were asked about their perspectives. Their involvement is further elucidated in the manuscript text.

The patients' and caregivers' perspective: In-hospital navigation aids for people with dementia- a qualitative study with a value sensitive design approach.

People with dementia (PwD) have serious difficulties orienting themselves in a hospital environment. In this qualitative study, we asked PwD and their informal caregivers about requirements for assistive technology when navigating in in-patient care settings. We aimed to provide user-centered recommendations for the development of an in-hospital navigation aid following a value sensitive design approach. We conducted semi-structured interviews with two stakeholder groups as potential future users of in-hospital navigation aids: PwD (n = 10, agemean = 83.9 years, MMSEmean = 21.2) and informal caregivers (n = 10, agemean = 75.9 years). The interviews were evaluated using qualitative content analysis in a multistage process involving six members of a self-help group for relatives of PwD as co-researchers. Independence and relief/respite were the most important values regarding assistive technology for PwD. Informal caregivers attributed greatest importance to safety and relief/respite. The underlying values of these stakeholder groups contribute to recommendations for designing new assistive technologies for patient-centered in-patient care: Assistive technology needs to overcome age- and disease-related limitations, and the resulting individual risks, while providing subsidiary assistance to maintain the desired independence of PwD for as long as possible.

Improved Bladder Tumor RNA Isolation from Archived Tissues Using Methylene Blue for Normalization, Multiplex RNA Hybridization, Sequencing and Subtyping.

Methylene blue (MB) is a dye used for histology with clinical importance and intercalates into nucleic acids. After MB staining of formalin fixed paraffin embedded (FFPE) muscle invasive bladder cancer (MIBC) and normal urothelium, specific regions could be microdissected. It is not known if MB influences RNA used for gene expression studies. Therefore, we analyzed MIBC using five different RNA isolation methods comparing patient matched FFPE and fresh frozen (FF) tissues pre-stained with or without MB. We demonstrate a positive impact of MB on RNA integrity with FF tissues using real time PCR with no interference of its chemical properties. FFPE tissues showed no improvement of RNA integrity, which we propose is due to formalin induced nucleotide crosslinks. Using direct multiplex RNA hybridization the best genes for normalization of MIBC and control tissues were identified from 34 reference genes. In addition, 5SrRNA and 5.8SrRNA were distinctive reference genes detecting <200 bp fragments important for mRNA analyses. Using these normalized RNAs from MB stained MIBC and applying multiplex RNA hybridization and mRNA sequencing, a minimal gene expression panel precisely identified luminal and basal MIBC tumor subtypes, important for diagnosis, prognosis and chemotherapy response.

Stakeholder involvement in dementia research: A qualitative approach with healthy senior citizens and providers of dementia care in Germany.

Engaging stakeholders in health-related research is becoming commonplace internationally and is increasingly considered best research practice to improve care management services. Many different groups have a stake in dementia care, but the evidence base for stakeholder involvement in dementia research is still small. The aim of this study was to explore views of two major stakeholder groups of dementia care in research priority setting and how they would want to be involved in dementia research. Group discussions were carried out with 47 participants divided into two groups: (a) healthy senior citizens and (b) providers of dementia care. Ensuing responses were analysed using descriptive content analysis. The main research interest of both groups was similar, but senior citizens and providers of dementia care varied in how they perceived the roles of researchers and stakeholders involved. Groups also differed with respect to the amount of time they would be willing to invest into research. The results contribute to our knowledge of group-specific stakeholder priorities and attitudes regarding participatory involvement in dementia research.

The Influence of Heart Rate Variability Biofeedback on Cardiac Regulation and Functional Brain Connectivity.

BACKGROUND: Heart rate variability (HRV) biofeedback has a beneficial impact on perceived stress and emotion regulation. However, its impact on brain function is still unclear. In this study, we aimed to investigate the effect of an 8-week HRV-biofeedback intervention on functional brain connectivity in healthy subjects. METHODS: HRV biofeedback was carried out in five sessions per week, including four at home and one in our lab. A control group played jump'n'run games instead of the training. Functional magnetic resonance imaging was conducted before and after the intervention in both groups. To compute resting state functional connectivity (RSFC), we defined regions of interest in the ventral medial prefrontal cortex (VMPFC) and a total of 260 independent anatomical regions for network-based analysis. Changes of RSFC of the VMPFC to other brain regions were compared between groups. Temporal changes of HRV during the resting state recording were correlated to dynamic functional connectivity of the VMPFC. RESULTS: First, we corroborated the role of the VMPFC in cardiac autonomic regulation. We found that temporal changes of HRV were correlated to dynamic changes of prefrontal connectivity, especially to the middle cingulate cortex, the left insula, supplementary motor area, dorsal and ventral lateral prefrontal regions. The biofeedback group showed a drop in heart rate by 5.2 beats/min and an increased SDNN as a measure of HRV by 8.6 ms (18%) after the intervention. Functional connectivity of the VMPFC increased mainly to the insula, the amygdala, the middle cingulate cortex, and lateral prefrontal regions after biofeedback intervention when compared to changes in the control group. Network-based statistic showed that biofeedback had an influence on a broad functional network of brain regions. CONCLUSION: Our results show that increased heart rate variability induced by HRV-biofeedback is accompanied by changes in functional brain connectivity during resting state.

Improving the depth of data quality or increasing confusion? Reflections on a data analysis involving members of a self-help group for relatives of people living with dementia.

BACKGROUND: Public involvement in research to improve data quality and to empower different stakeholders is good scientific practice, but rarely implemented across all research phases. OBJECTIVE: This article reports on an attempt to involve members of a self-help group for relatives of people living with dementia as co-researchers in the data analysis in a short-term format. METHODS: One researcher identified statements about assistive technologies from 17 interviews with people living with dementia and informal caregivers. Two researchers and six co-researchers independently assigned pre-defined values to these statements. Subsequently, we compared the values of the researchers and co-researchers. RESULTS: The members of the self-help group identified four original values not considered by the researchers: consent, inclusion, participation and respect. DISCUSSION: The involvement of co-researchers led to an improvement in the depth of data quality through the joint identification of values concerning assistive technology. Language barriers between researchers, co-researchers and interview participants impeded the data analysis. CONCLUSION: The challenges and benefits of a participatory data analysis shown here can provide a basis for recommendations for target group-specific research involvement. Our recommendations relate to the recruitment of co-researchers, requirements for conducting a participatory data analysis and the participation degree of people involved. PATIENT OR PUBLIC CONTRIBUTION: The group of co-researchers participating in the data analysis consisted of relatives of people living with dementia.

Functional consequences of acute tryptophan depletion on raphe nuclei connectivity and network organization in healthy women.

Previous research on central nervous serotonin (5-HT) function provided evidence for a substantial involvement of 5-HT in the regulation of brain circuitries associated with cognitive and affective processing. The underlying neural networks comprise core subcortical/cortical regions such as amygdala and medial prefrontal cortex, which are assumed to be modulated amongst others by 5-HT. Beside the use of antidepressants, acute tryptophan depletion (ATD) is a widely accepted technique to manipulate of 5-HT synthesis and its respective metabolites in humans by means of a dietary and non-pharmacological tool. We used a double-blind, randomized, cross-over design with two experimental challenge conditions, i.e. ATD and tryptophan (TRP) supplementation (TRYP+) serving as a control. The aim was to perturb 5-HT synthesis and to detect its impact on brain functional connectivity (FC) of the upper serotonergic raphe nuclei, the amygdala and the ventromedial prefrontal cortex as well as on network organization using resting state fMRI. 30 healthy adult female participants (age: M â€‹= â€‹24.5 â€‹± â€‹4.4 â€‹yrs) were included in the final analysis. ATD resulted in a 90% decrease of TRP in the serum relative to baseline. Compared to TRYP â€‹+ â€‹for the ATD condition a significantly lower FC of the raphe nucleus to the frontopolar cortex was detected, as well as greater functional coupling between the right amygdala and the ventromedial prefrontal cortex. FC of the raphe nucleus correlated significantly with the magnitude of TRP changes for both challenge conditions (ATD & TRYP+). Network-based statistical analysis using time series from 260 independent anatomical ROIs revealed significantly greater FC after ATD compared to TRYP+ in several brain regions being part of the default-mode (DMN) and the executive-control networks (ECN), but also of salience or visual networks. Finally, we observed an impact of ATD on the rich-club organization in terms of decreased rich-club coefficients compared to TRYP+. In summary we could confirm previous findings that the putative decrease in brain 5-HT synthesis via ATD significantly alters FC of the raphe nuclei as well as of specific subcortical/cortical regions involved in affective, but also in cognitive processes. Moreover, an ATD-effect on the so-called rich-club organization of some nodes with the high degree was demonstrated. This may indicate effects of brain 5-HT on the integration of information flow from several brain networks.

Resilience and cortical thickness: a MRI study.

Resilience is defined as the psychological resistance which enables the processing of stress and adverse life events and thus constitutes a key factor for the genesis of psychiatric illness. However, little is known about the morphological correlates of resilience in the human brain. Hence, the aim of this study is to examine the neuroanatomical expression of resilience in healthy individuals. 151 healthy subjects were recruited and had to complete a resilience-specific questionnaire (RS-11). All of them underwent a high-resolution T1-weighted MRI in a 3T scanner. Fine-grained cortical thickness was analyzed using FreeSurfer. We found a significant positive correlation between the individual extent of resilience and cortical thickness in a right hemispherical cluster incorporating the lateral occipital cortex, the fusiform gyrus, the inferior parietal cortex as well as the middle and inferior temporal cortex, i.e., a reduced resilience is associated with a decreased cortical thickness in these areas. We lend novel evidence for a direct linkage between psychometric resilience and local cortical thickness. Our findings in a sample of healthy individuals show that a lower resilience is associated with a lower cortical thickness in anatomical areas are known to be involved in the processing of emotional visual input. These regions have been demonstrated to play a role in the pathogenesis of stress and trauma-associated disorders. It can thus be assumed that neuroanatomical variations in these cortical regions might modulate the susceptibility for the development of stress-related disorders.

Connectomics-Based Functional Network Alterations in both Depressed Patients with Suicidal Behavior and Healthy Relatives of Suicide Victims.

Understanding the neural mechanisms of suicidal behavior is crucial. While regional brain alterations have previously been reported, knowledge about brain functional connectomics is currently limited. Here, we investigated differences in global topologic network properties and local network-based functional organization in both suicide attempters and suicide relatives. Two independent samples of depressed suicide attempters (N = 42), depressed patient controls (N = 43), healthy controls (N = 66) as well as one sample of healthy relatives of suicide victims (N = 16) and relatives of depressed patients (N = 16) were investigated with functional magnetic resonance imaging in the resting-state condition. Graph theory analyses were performed. Assortativity, clustering coefficients, global efficiency, and rich-club coefficients were calculated. A network-based statistic approach was finally used to examine functional connectivity matrices. In comparison to healthy controls, both patient groups showed significant reduction in assortativity, and decreased functional connectivity in largely central and posterior brain networks. Suicide attempters only differed from patient controls in terms of higher rich-club coefficients for the highest degree nodes. Compared to patient relatives and healthy controls, suicide relatives showed reduced assortativity, reduced clustering coefficients, increased global efficiency, and increased rich-club coefficients for the highest degree nodes. Suicide relatives also showed reduced functional connectivity in one anterior and one posterior sub-network in comparison to healthy controls, and in a largely anterior brain network in comparison to patient relatives. In conclusion, these results suggest that the vulnerability to suicidal behavior may be associated with heritable deficits in global brain functioning - characterized by weak resilience and poor segregation - and in functional organization with reduced connectivities affecting the ventral and dorsal prefrontal cortex, the anterior cingulate, thalamus, striatum, and possibly the insula, fusiform gyrus and the cerebellum.

TRIM58 Restrains Intestinal Mucosal Inflammation by Negatively Regulating TLR2 in Myeloid Cells.

Balanced control of innate immune signaling in the intestine represents an important host defense mechanism to avoid inappropriate responses that may exacerbate mucosal injury in acute inflammation. In this study, we report that TRIM58, a RING E3-ubiquitin ligase, associates with TLR2. The interaction was found in a yeast two-hybrid screen (human leukocyte and mononuclear library) and confirmed by coimmunoprecipitation of tagged and endogenous proteins. TRIM58 was predominantly expressed by murine and human myeloid-derived cells. Stimulation with a TLR2 ligand modulated TRIM58 synthesis in myeloid cells. Overexpression of TRIM58, but only in presence of the RING domain, promoted proteasome-dependent degradation of TLR2, inhibiting its signaling activity. Genetic deletion of Trim58 in mice (Trim58 -/-) led to impaired resolution of acute dextran sodium sulfate-induced colitis, which was characterized by delayed recovery from colonic injury and associated with enhanced expression of TLR2 protein and proinflammatory cyto/chemokine production in inflamed colons. Using myeloid cell-specific deletion of Trim58 in mice, we demonstrated that the myeloid cell compartment was responsible for early colitis acceleration in Trim58 deficiency. In vitro studies revealed that Trim58 -/- myeloid cells, which showed constitutive upregulation of TLR2 protein, overreacted to a proinflammatory milieu (TNF-α and IFN-γ) with increased IL-1ß protein production, which mechanistically depended on Tlr2 Finally, we found that TRIM58 mRNA and protein expression levels were reduced in colonic specimens from patients with ulcerative colitis. In conclusion, we identify TRIM58 as a novel negative mediator of innate immune control and mucosal homeostasis via TLR2 signaling. Dysfunction of TRIM58 in myeloid cells may contribute to ulcerative colitis pathogenesis.

Effect of an eight-week smartphone-guided HRV-biofeedback intervention on autonomic function and impulsivity in healthy controls.

A large body of scientific studies suggest a close relationship between increased vagal function and better cognitive performance. OBJECTIVE: In the current study, we investigated the association between autonomic function and behavioral impulsivity. We hypothesized that heart rate variability (HRV) biofeedback training increases HRV and enhances inhibitory control. APPROACH: A total of 28 healthy participants were recruited. After drop-out, 14 participants completed an eight-week HRV biofeedback training with five training sessions per week including one session at the clinic's laboratory and four sessions at home using a mobile application running on their smartphone. Ten control subjects matched with respect to age and gender played a mobile game according to the same schedule as the biofeedback group. The assessment of autonomic status and the stop-signal task were conducted before the beginning of the training (T1) and after finishing the schedule (T2). MAIN RESULTS: We found a relationship of reaction times in the stop-signal task and standard HRV as well as cardiorespiratory indices. After biofeedback training, short-term HRV and baroreflex function significantly increased by 33% (CI [2%, 64%], p  < 0.05) and 21% (CI [5%, 36%], p  < 0.05), respectively. The performance in the stop-signal task was not affected by the biofeedback intervention. Compared to the changes of autonomic indices in the control group, only a decrease of skin conductance levels in the biofeedback group remained statistically significant. SIGNIFICANCE: Our results indicate that a smartphone-based HRV biofeedback intervention can be applied to improve cardiovagal function in healthy subjects. Although higher HRV was associated with higher levels of inhibitory control, HRV biofeedback had no effect on measures of impulsivity.

Checking and washing rituals are reflected in altered cortical thickness in obsessive-compulsive disorder.

There is growing evidence for structural brain alterations in obsessive-compulsive disorder (OCD). The overall picture is however rather heterogeneous. To detect meaningful associations between clinical symptom profiles and structural alterations, we applied a classification approach, the k-means cluster analysis on clinical data, i.e., the Obsessive Compulsive Inventory-Revised (OCI-R) questionnaire. 73 OCD patients were assigned to three distinct symptom profiles. Using structural MRI and surface-based morphometric analysis (SBM), we compared cortical thickness between all OCD patients and 69 matched healthy subjects as well as among patients according to three symptom profiles. The total sample of OCD patients exhibited a thicker cortex in the pre-supplementary motor cortex (pre-SMA), dorsomedial prefrontal (DMPFC), anterior cingulate cortex and in the right anterior insula. Comparing patients of the three symptom clusters, a subgroup of OCD patients with a specific symptom profile was identified, which showed a thicker cortex in pre-SMA/DMPFC and in the contralateral primary motor cortex. In contrast to both other subgroups, patients in this group were mainly characterized by the predominance of a combination of checking and washing rituals. The other two OCD symptom subgroups showed comparable cortical thickness to healthy controls. Higher cortical thickness in regions of the motor circuitry seems to be related to motor activity-induced neuroplasticity in a specific group of OCD patients. Thicker anterior insular cortex in the total sample of patients points toward a more general pathophysiological process in OCD and potentially indicates abnormal interoceptive processing in OCD.

The relationship between heart rate and functional connectivity of brain regions involved in autonomic control.

The peripheral autonomic nervous system (ANS) adjusts the heart rate (HR) to intrinsic and extrinsic demands. It is controlled by a group of functionally connected brain regions assembling the so-called central autonomic network (CAN). More specifically, forebrain cortical regions, limbic and brainstem structures within the CAN have been identified as important components of circuits involved in HR regulation. The present study aimed to investigate whether functional connectivity (FC) between these regions varies in subjects with different heart rates. Thus, 84 healthy subjects were separated according to their HR in slow, medium and fast. We observed a direct association between HR and FC in CAN regions, where stronger FC was related to slower HR. This relationship, however, is non-linear, follows an exponential course and is not restricted to CAN areas only. The network-based analysis (NBS) using time series from 262 independent anatomical ROIs revealed significantly increased functional connectivity in subjects with slow HR compared to subjects with fast HR mainly in regions being part of the salience network, but also of the default-mode network. We additionally simulated the effect of aliasing on the functional connectivity using several TRs and heart rates to exclude the possibility that FC differences might be due to different aliasing effects in the data. The result of the simulation indicated that aliasing cannot explain our findings. Thus, present results imply a functionally meaningful coupling between FC and HR that need to be accounted for in future studies. Moreover, given the established link between HR and emotional, cognitive and social processes, present findings may also be considered to explain individual differences in brain activation or connectivity when using corresponding paradigms in the MR scanner to investigate such processes.

Activation of brainstem and midbrain nuclei during cognitive control in medicated patients with schizophrenia.

Evidence suggests that cognitive control functions as well as the underlying brain network, anchored by the prefrontal cortex (PFC) and the dorsal anterior cingulate cortex (dACC), are dysfunctional in schizophrenia. Catecholamine producing midbrain and brainstem nuclei are densely connected with the PFC and dACC and exert profound contributions to cognitive control processes. Dysfunctions within the underlying neurotransmitter systems are considered to play a central role in the occurrence of various symptoms of schizophrenia. We sought to investigate the putatively abnormal activation pattern of the dopaminergic midbrain nuclei, that is, ventral tegmental area (VTA) and substantia nigra as well as that of the noradrenergic locus coeruleus (LC) in patients with schizophrenia during cognitive control. A total of 28 medicated patients and 27 healthy controls were investigated with the manual version of the Stroop task using event-related fMRI. The main finding was a reduced BOLD activation in the VTA during both Stroop task conditions in patients in comparison to controls, which correlated significantly with the degree of negative symptoms. We further detected a comparable LC activation in in patients and healthy controls. However, in controls LC activation was significantly correlated with the Stroop interference time, which was not observed in patients. The finding of reduced VTA activation in schizophrenia patients lends further support to the assumed dysfunction of the DA system in schizophrenia. In addition, despite comparable LC activation, the nonsignificant correlation with the Stroop interference time might indicate altered LC functioning in schizophrenia and, thus, needs further investigations.

The Use of Physiological Signals in Brainstem/Midbrain fMRI.

Brainstem and midbrain nuclei are closely linked to cognitive performance and autonomic function. To advance the localization in this area, precise functional imaging is fundamental. In this study, we used a sophisticated fMRI technique as well as physiological recordings to investigate the involvement of brainstem/midbrain nuclei in cognitive control during a Stroop task. The temporal signal-to-noise ratio (tSNR) increased due to physiological noise correction (PNC) especially in regions adjacent to arteries and cerebrospinal fluid. Within the brainstem/cerebellum template an average tSNR of 68 ± 16 was achieved after the simultaneous application of a high-resolution fMRI, specialized co-registration, and PNC. The analysis of PNC data revealed an activation of the substantia nigra in the Stroop interference contrast whereas no significant results were obtained in the midbrain or brainstem when analyzing uncorrected data. Additionally, we found that pupil size indicated the level of cognitive effort. The Stroop interference effect on pupillary responses was correlated to the effect on reaction times (R 2 = 0.464, p < 0.05). When Stroop stimuli were modulated by pupillary responses, we observed a significant activation of the LC in the Stroop interference contrast. Thus, we demonstrated the beneficial effect of PNC on data quality and statistical results when analyzing neuronal responses to a cognitive task. Parametric modulation of task events with pupillary responses improved the model of LC BOLD activations in the Stroop interference contrast.

Towards response success prediction: An integrative approach using high-resolution fMRI and autonomic indices.

Brainstem and midbrain nuclei are closely linked to effective cognitive performance and autonomic function. In the present study, we aimed to investigate indices of successful and unsuccessful response inhibition paying particular attention to the interplay between locus coeruleus (LC), ventral tegmental area (VTA)/substantia nigra (SN) and, most importantly, peripheral markers. We aimed to get insight in the predictive value of neural and physiological signals in response inhibition. A total of 35 healthy controls were recruited from the local community and a typical task of behavioral response inhibition (Go/No-Go paradigm) was applied. We used high-resolution fMRI, advanced brainstem analyses and specifically corrected for respiratory signal and cardiac noise. Our main results characterize specific neural activation patterns during successful and unsuccessful response inhibition especially comprising the anterior cingulate as well as the medial and lateral prefrontal cortex. A significant activation of the dopaminergic nuclei (VTA/SN) was found during error processing, but not during response inhibition. Most remarkably, specific neural activation patterns (i.e., dorsal anterior cingulate cortex) as well as accompanying autonomic indices (i.e., skin conductance response (SCR)) were identified to hold predictive information on an individual's performance. In summary, the importance of the VTA/SN during error processing was shown. Furthermore, autonomic indices and specific neural activation patterns may contain valuable information to predict task performance.

Neuroimaging-informed phenotypes of suicidal behavior: a family history of suicide and the use of a violent suicidal means.

The identification of brain markers of suicidal risk is highly expected. However, neuroimaging studies have yielded mixed results, possibly due to phenotypic heterogeneity. In the present study, we addressed this issue using structural brain imaging. First, two independent samples of suicide attempters (n = 17 in Montreal, 32 in Jena), patient controls (n = 26/34), and healthy controls (n = 66/34) were scanned with magnetic resonance imaging. Groups were compared with FSL. We then reviewed the literature and run a GingerALE meta-analysis of 12 structural imaging studies comparing suicide attempters and patient controls with whole-brain analyses (n = 693). Finally, we explored the potential contribution of two variables previously associated with biological/cognitive deficits: a family history of suicide (FHoS), and the use of a violent suicidal means (VSM). Here, we added two groups of healthy first-degree biological relatives of suicide victims and depressed patients (n = 32). When comparing all suicide attempters and controls, very limited between-group differences were found in the two samples, and none in the meta-analysis. In contrast, a FHoS was associated with reduced volumes in bilateral temporal regions, right dorsolateral prefrontal cortex, and left putamen, several of these differences being observed across groups. VSM was associated with increased bilateral caudate (and left putamen) volumes. Some morphometric variations in cortico-subcortical networks may therefore be endophenotypes increasing the suicidal vulnerability, while others (notably in striatum) may modulate action selection. These results therefore confirm at the neural level two phenotypes at high lethal risk with a strong biological background, and uncover motives of heterogeneous findings in neuroimaging studies of suicidal behavior.