Background In a recent cross-sectional study, we highlighted psychosocial resilience factors asso... more Background In a recent cross-sectional study, we highlighted psychosocial resilience factors associated with good mental health during the first COVID-19-lockdown. However, dynamic concepts of resilience suggest that people’s response to adversity can change over time. To better understand the emergence of resilience, we here examined individual dynamics of stressor resilience during the COVID-19 pandemic. Methods In a longitudinal experience sampling design, participants (N=200) completed six weekly questionnaires assessing current stressor exposure, mental health burden, and resilience factors. We used linear mixed models to investigate within- and between-subject associations between stressor resilience and protective factors. Results Weekly stressor resilience scores were positively associated with subject-level variation in the resilience factors positive appraisal use, positive appraisal of the COVID-19 pandemic, and general self-efficacy (ps<.05). Time-lagged analyses showed no prediction of stressor resilience by resilience factor use in the preceding week. Stressor exposure positively predicted behavioural coping use during the next week (p<.02). Conclusion Observed fluctuations in positive appraisal use and general self-efficacy within individuals support the notion that processes of resilience are not stable across time. The time-delayed effect of stressor exposure on behavioural coping use might indicate an early mechanism of stress inoculation, by which stress improves future coping strategies.
The current Corona pandemic is not only a threat to physical health. First data from China and th... more The current Corona pandemic is not only a threat to physical health. First data from China and the United Kingdom indicate that symptoms of anxiety and depression and perceptions of stress rise significantly as a consequence of the pandemic. There are also anecdotal reports in the general media of increased domestic violence, divorce and suicide rates. Hence, the Corona crisis is also a mental health crisis. Threats to public mental health are likely to further increase with the spread of the virus across the world and the potentially severe economic, societal and political side effects of the pandemic. In this situation, there is urgent need for knowledge about factors that can protect mental health in this world-wide crisis and that can be harnessed in the service of public mental health promotion. DynaCORE-C attempts to identify these protective factors (resilience factors) with the help of an internet-based cross-sectional questionnaire survey for adults available in multiple languages. Our dependent variable is resilience. In keeping with current conceptualizations of this construct (Bonanno et al., 2015; Kalisch et al., 2017), we define resilience as an outcome of good mental health despite exposure to adversity (outcome-based resilience) and measure it by relating mental health outcomes to experienced stressors (Kalisch et al., 2015), which we extensively sample. That is, we do not rely on resilience questionnaires to obtain our dependent variable. In defining our hypotheses about independent variables (resilience factors), we focus on modifiable factors that can be targeted by prevention measures. Specifically, we hypothesize that social support, an increase in social support during the Corona crisis, optimism, general self-efficacy, good stress recovery, positive appraisal style (primary hypothesis), positive appraisal specifically of the Corona crisis, and behavioral coping are positively associated with resilience (outcome), while neuroticism is negatively associated with resilience. We also hypothesiz [...]
Background: Alzheimer's disease (AD) is the most common cause of dementia. Brain calcifications, ... more Background: Alzheimer's disease (AD) is the most common cause of dementia. Brain calcifications, as well as intracranial neoplasms, are also related with cognitive disorders. The association of these 3 conditions is very rare and to our knowledge not described yet. Objective: To describe a case of AD with a typical presentation associated with diffuse encephalic calcifications and a left frontal lobe meningeoma. Patient and Methods: A 79-year-old woman is reported. Diagnosis of AD was based on neurological examination, psychometric tests, neuroimaging findings, and exclusion of secondary dementia. She developed seizures at 9-year evolution of disease. A low thyroid stimulating hormone (TSH) level was detected and attributed to chronic use of amiodarone. Mini-Mental State Examination score was 7. Impaired verbal fluency and span digit test performance was observed. Severe perseveration and ecolalia were present. CT scan showed calcifications addressing cerebellum, basal ganglia, subcortical white matter, and occipital cortex. A meningeoma with left frontal lobe compression was also seen. Conclusion: Cognitive decline in AD may be in this case aggravated by simultaneous presence of other conditions such as diffuse encephalic calcifications and a frontal lobe meningeoma.
Anxiety reduction through mere expectation of anxiolytic treatment effects (placebo anxiolysis) h... more Anxiety reduction through mere expectation of anxiolytic treatment effects (placebo anxiolysis) has enormous clinical importance. Recent behavioral and electrophysiological data suggest that placebo anxiolysis involves reduced vigilance and enhanced internalization of attention; however, the underlying neurobiological mechanisms are not yet clear. Given the fundamental function of intrinsic connectivity networks (ICNs) in basic cognitive processes, we investigated ICN activity patterns associated with externally and internally directed mental states under the influence of an anxiolytic placebo medication. Based on recent findings, we specifically analyzed the functional role of the rostral anterior cingulate cortex (rACC) in coordinating placebo-dependent cue-related (phasic) and cue-unrelated (sustained) network activity. Under placebo, we observed a down-regulation of the entire salience network (SN), particularly in response to threatening cues. The rACC exhibited enhanced cue-unrelated functional connectivity (FC) with the SN, which correlated with reductions in tonic arousal and anxiety. Hence, apart from the frequently reported modulation of aversive cue responses, the rACC appears to be crucially involved in exerting a tonically dampening control over salience-responsive structures. In line with a more internally directed mental state, we also found enhanced FC within the default mode network (DMN), again predicting reductions in anxiety under placebo.
Neurorehabilitation and Neural Repair, Mar 16, 2007
To understand neural reorganization of response regulation after stroke, a 54-year-old woman with... more To understand neural reorganization of response regulation after stroke, a 54-year-old woman with a chronic left thalamic stroke performed a task requiring decisions about the directionality of an arrow during cerebral functional magnetic resonance imaging. Her performance was compared to 13 matched healthy control subjects. Her behavioral responses were slower but as accurate. Bilateral frontal activations were observed in the right medial frontal gyrus (BA 9), left superior frontal gyrus (BA 45), and left frontal rectus gyrus (BA 11). Activation in the right medial frontal gyrus, along with activity in close proximity to the anterior cingulate cortex, was observed, which may reflect reorganization of activity after the loss of function of the anterior cingulate cortex.
medRxiv (Cold Spring Harbor Laboratory), Aug 21, 2020
Deep learning approaches can uncover complex patterns in data. In particular, variational autoenc... more Deep learning approaches can uncover complex patterns in data. In particular, variational autoencoders (VAEs) achieve this by a non-linear mapping of data into a low-dimensional latent space. Motivated by an application to psychological resilience in the Mainz Resilience Project (MARP), which features intermittent longitudinal measurements of stressors and mental health, we propose an approach for individualized, dynamic modeling in this latent space. Specifically, we utilize ordinary differential equations (ODEs) and develop a novel technique for obtaining person-specific ODE parameters even in settings with a rather small number of individuals and observations, incomplete data, and a differing number of observations per individual. This technique allows us to subsequently investigate individual reactions to stimuli, such as the mental health impact of stressors. A potentially large number of baseline characteristics can then be linked to this individual response by regularized regression, e.g., for identifying resilience factors. Thus, our new method provides a way of connecting different kinds of complex longitudinal and baseline measures via individualized, dynamic models. The promising results obtained in the exemplary resilience application indicate that our proposal for dynamic deep learning might also be more generally useful for other application domains. NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
This fMRI study studied age-related differences in neural activities during response regulation. ... more This fMRI study studied age-related differences in neural activities during response regulation. Twenty-one male participants from two age groups, a younger group and an older group (mean ages: 29.9 and 65.2 years, respectively), were scanned while performing a task with response compatibility manipulation. They were presented with a sequence of arrowheads that pointed either upward or downward. In the "Response Compatible" condition, they were required to press an up or a down button consistent with the direction of the arrowhead. In the "Response Incompatible" condition, they were required to press the button opposite to the arrowhead direction so that an upward arrow should elicit a down response, and vice versa. Findings showed age-related differences in response regulation in several brain regions, including the right frontal, the right cingulate, and the left inferior parietal cortexes. The findings suggested a higher level of neural activity in the right prefrontal and left inferior parietal regions during response regulation for the older adults than for the younger adults.
Learning fear via the experience of contingencies between a conditioned stimulus (CS) and an aver... more Learning fear via the experience of contingencies between a conditioned stimulus (CS) and an aversive unconditioned stimulus (US) is often assumed to be fundamentally different from learning fear via instructions. An open question is whether fear-related brain areas respond differently to experienced CS-US contingencies than to merely instructed CS-US contingencies. Here, we contrasted two experimental conditions where subjects were instructed to expect the same CS-US contingencies while only one condition was characterized by prior experience with the CS-US contingency. Using multivoxel pattern analysis of fMRI data, we found CS-related neural activation patterns in the right amygdala (but not in other fear-related regions) that dissociated between whether a CS-US contingency had been instructed and experienced versus merely instructed. A second experiment further corroborated this finding by showing a categoryindependent neural response to instructed and experienced, but not merely instructed, CS presentations in the human right amygdala. Together, these findings are in line with previous studies showing that verbal fear instructions have a strong impact on both brain and behavior. However, even in the face of fear instructions, the human right amygdala still shows a separable neural pattern response to experience-based fear contingencies.
International Journal of Geriatric Psychiatry, Mar 1, 2004
Memory difficulty is one of the most common complaints of older people, with or without psychiatr... more Memory difficulty is one of the most common complaints of older people, with or without psychiatric conditions. It is therefore of utmost important to understand how normal ageing process impacts upon prose memory so as to gain insight into ways to differentiate pathological vs normal age-related changes of the recall of prose observed among older people. To understand the differential age-related change of prose memory in older Hong Kong Chinese of higher and lower education. Forty-eight normal, healthy Cantonese-speaking Chinese were recruited. Seventeen of them were younger, highly educated participants. Among the 31 older people recruited, 19 of them received education comparable with the younger participants and 12 were older people of low education. A prose passage was constructed to measure the different processes of prose memory, including learning efficiency, rate of forgetting, recall accuracy, accuracy of temporal sequence of information recalled, distortions, and recognition memory. As expected, ageing affected all the processes of prose memory measured, except the rate of forgetting. Apart from learning efficiency and rate of forgetting, education was observed to modify the effect of ageing on all the processes studied. Changes of prose memory associated with ageing and the differential effect of education on prose recall among older people were discussed. The findings seem to suggest that prose memory is a multifaceted construct.
Motivated by the recent replicability crisis we tested replicability of functional magnetic reson... more Motivated by the recent replicability crisis we tested replicability of functional magnetic resonance imaging (fMRI) group activations in two independent samples. An identical behavioral and fMRI test battery for the longitudinal investigation of stress resilience mechanisms was developed for the Mainz Resilience Project (MARP) and conducted in a discovery (N ¼ 54) and a replication sample (N ¼ 103). The test battery consisted of a stress reactivity task, a reward sensitivity task, a fear conditioning and extinction paradigm, two volitional reappraisal tasks and an emotional interference inhibition task. Replicability of group activations was tested with the Jaccard index and the Intra Class Correlation (ICC). Overall, we observed good to excellent replicability of activations at the whole brain level. Only a minority of contrasts showed unsatisfactory replicability. Replicability at the level of individual regions of interest (ROIs) was generally lower. Tasks with stronger activation in the discovery sample showed better replicability.
BACKGROUND Stress-related mental disorders are highly prevalent and pose a substantial burden on ... more BACKGROUND Stress-related mental disorders are highly prevalent and pose a substantial burden on individuals and society. Improving strategies for the prevention and treatment of mental disorders requires a better understanding of their risk and resilience factors. This multicenter study aims to contribute to this endeavor by investigating psychological resilience in healthy but susceptible young adults over 9 months. Resilience is conceptualized in this study as the maintenance of mental health or quick recovery from mental health perturbations upon exposure to stressors, assessed longitudinally via frequent monitoring of stressors and mental health. OBJECTIVE This study aims to investigate the factors predicting mental resilience and adaptive processes and mechanisms contributing to mental resilience and to provide a methodological and evidence-based framework for later intervention studies. METHODS In a multicenter setting, across 5 research sites, a sample with a total target size of 250 young male and female adults was assessed longitudinally over 9 months. Participants were included if they reported at least 3 past stressful life events and an elevated level of (internalizing) mental health problems but were not presently affected by any mental disorder other than mild depression. At baseline, sociodemographic, psychological, neuropsychological, structural, and functional brain imaging; salivary cortisol and α-amylase levels; and cardiovascular data were acquired. In a 6-month longitudinal phase 1, stressor exposure, mental health problems, and perceived positive appraisal were monitored biweekly in a web-based environment, while ecological momentary assessments and ecological physiological assessments took place once per month for 1 week, using mobile phones and wristbands. In a subsequent 3-month longitudinal phase 2, web-based monitoring was reduced to once a month, and psychological resilience and risk factors were assessed again at the end of the 9-month period. In addition, samples for genetic, epigenetic, and microbiome analyses were collected at baseline and at months 3 and 6. As an approximation of resilience, an individual stressor reactivity score will be calculated. Using regularized regression methods, network modeling, ordinary differential equations, landmarking methods, and neural net–based methods for imputation and dimension reduction, we will identify the predictors and mechanisms of stressor reactivity and thus be able to identify resilience factors and mechanisms that facilitate adaptation to stressors. RESULTS Participant inclusion began in October 2020, and data acquisition was completed in June 2022. A total of 249 participants were assessed at baseline, 209 finished longitudinal phase 1, and 153 finished longitudinal phase 2. CONCLUSIONS The Dynamic Modelling of Resilience–Observational Study provides a methodological framework and data set to identify predictors and mechanisms of mental resilience, which are intended to serve as an empirical foundation for future intervention studies. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/39817
Background: The rising prevalence of stress-related mental and physical disorders over the past d... more Background: The rising prevalence of stress-related mental and physical disorders over the past decades, and more recently in connection to the COVID-19 pandemic, highlights the need for a better understanding of stress-protective factors (resilience factors) Resilience has been conceptualised as the maintenance or quick recovery of mental health following exposure to adversity By studying psycho-social factors that influence resilience in the context of the COVID-19 pandemic, it was possible to examine population-wide responses to stressors of unusually similar nature Methods: In a first interim analysis of an international resilience study we examined data from 5000 European adults collected during the first phases of pandemic-related movement and contact restrictions (‘lockdown’) Linear regression, regularised regression, and mediation analyses were employed to compare the influence of nine potential resilience factors according to preregistered hypotheses (osf io/r6btn) Results: All hypothesized resilience factors were significantly associated with resilience as an outcome Compared to other resilience factors, positive appraisal of the COVID-19 pandemic showed the strongest effect Results confirmed our primary hypothesis that general positive appraisal style (PAS) is positively associated with resilience, and further revealed that PAS mediates the positive influence of perceived social support on resilience Discussion: The investigated resilience factors provide promising targets for health interventions that aim to improve stress resilience in general or in the face of prolonged pandemic-related adversity To improve intervention planning, future research should also investigate the influence of socio-demographic factors on resilience factor use and efficacy, as well as the dynamics of time-variant resilience development in response to stressors exposure
bioRxiv (Cold Spring Harbor Laboratory), Nov 17, 2018
Resilience is the maintenance or rapid recovery of mental health during and after stressor exposu... more Resilience is the maintenance or rapid recovery of mental health during and after stressor exposure. It is becoming increasingly clear that resilience results from a complex and dynamic process of adaptation to stressors involving the biological, psychological and social levels. Positive appraisal style theory of resilience (PASTOR) claims that the common final pathway to maintained mental health lies in the non-negative (non-catastrophizing, nonpessimistic) appraisal of potential stressors, permitting the organism to fine-tune stress responses to optimal levels, thus avoiding unnecessary stress, inefficient deployment of resources and concomitant deleterious allostatic load effects. Successful adaptation consists in developing or strengthening a positive appraisal style. Another key element of PASTOR is that a positive appraisal style is strongly determined by the efficacy and efficiency of the neural and cognitive processes that underlie positive stressor appraisal. We here present a combined behavioral and functional magnetic resonance imaging (fMRI) battery designed to assess such processes repeatedly in longitudinal settings. The battery includes tests of stress reactivity and recovery, reward sensitivity, safety learning and memory in the context of fear conditioning and extinction, volitional situation-focused reappraisal, volitional self-focused reappraisal, and emotional interference inhibition, along with structural MRI and resting-state MRI scans. A detailed description of the battery methods is provided. The feasibility of the battery was successfully tested in N=55 healthy subjects; group results of the individual tasks largely replicate existing literature.
Dopamine dysfunction is associated with a wide range of neuropsychiatric disorders commonly treat... more Dopamine dysfunction is associated with a wide range of neuropsychiatric disorders commonly treated pharmacologically or invasively. Recent studies provide evidence for a nonpharmacological and noninvasive alternative that allows similar manipulation of the dopaminergic system: transcranial direct current stimulation (tDCS). In rodents, tDCS has been shown to increase neural activity in subcortical parts of the dopaminergic system, and recent studies in humans provide evidence that tDCS over prefrontal regions induces striatal dopamine release and affects reward-related behavior. Based on these findings, we used fMRI in healthy human participants and measured the fractional amplitude of low-frequency fluctuations to assess spontaneous neural activity strength in regions of the mesostriatal dopamine system before and after tDCS over prefrontal regions (n ϭ 40, 22 females). In a second study, we examined the effect of a single dose of the dopamine precursor levodopa (L-DOPA) on mesostriatal fractional amplitude of low-frequency fluctuation values in male humans (n ϭ 22) and compared the results between both studies. We found that prefrontal tDCS and L-DOPA both enhance neural activity in core regions of the dopaminergic system and show similar subcortical activation patterns. We furthermore assessed the spatial similarity of whole-brain statistical parametric maps, indicating tDCS-andL-DOPA-inducedactivation,andϾ100neuronalreceptorgeneexpressionmapsbasedontranscriptionaldatafromtheAllenInstitute forBrainScience.Inlinewithaspecificactivationofthedopaminergicsystem,wefoundthatbothinterventionspredominantlyactivatedregions with high expression levels of the dopamine receptors D2 and D3.
Background In a recent cross-sectional study, we highlighted psychosocial resilience factors asso... more Background In a recent cross-sectional study, we highlighted psychosocial resilience factors associated with good mental health during the first COVID-19-lockdown. However, dynamic concepts of resilience suggest that people’s response to adversity can change over time. To better understand the emergence of resilience, we here examined individual dynamics of stressor resilience during the COVID-19 pandemic. Methods In a longitudinal experience sampling design, participants (N=200) completed six weekly questionnaires assessing current stressor exposure, mental health burden, and resilience factors. We used linear mixed models to investigate within- and between-subject associations between stressor resilience and protective factors. Results Weekly stressor resilience scores were positively associated with subject-level variation in the resilience factors positive appraisal use, positive appraisal of the COVID-19 pandemic, and general self-efficacy (ps<.05). Time-lagged analyses showed no prediction of stressor resilience by resilience factor use in the preceding week. Stressor exposure positively predicted behavioural coping use during the next week (p<.02). Conclusion Observed fluctuations in positive appraisal use and general self-efficacy within individuals support the notion that processes of resilience are not stable across time. The time-delayed effect of stressor exposure on behavioural coping use might indicate an early mechanism of stress inoculation, by which stress improves future coping strategies.
The current Corona pandemic is not only a threat to physical health. First data from China and th... more The current Corona pandemic is not only a threat to physical health. First data from China and the United Kingdom indicate that symptoms of anxiety and depression and perceptions of stress rise significantly as a consequence of the pandemic. There are also anecdotal reports in the general media of increased domestic violence, divorce and suicide rates. Hence, the Corona crisis is also a mental health crisis. Threats to public mental health are likely to further increase with the spread of the virus across the world and the potentially severe economic, societal and political side effects of the pandemic. In this situation, there is urgent need for knowledge about factors that can protect mental health in this world-wide crisis and that can be harnessed in the service of public mental health promotion. DynaCORE-C attempts to identify these protective factors (resilience factors) with the help of an internet-based cross-sectional questionnaire survey for adults available in multiple languages. Our dependent variable is resilience. In keeping with current conceptualizations of this construct (Bonanno et al., 2015; Kalisch et al., 2017), we define resilience as an outcome of good mental health despite exposure to adversity (outcome-based resilience) and measure it by relating mental health outcomes to experienced stressors (Kalisch et al., 2015), which we extensively sample. That is, we do not rely on resilience questionnaires to obtain our dependent variable. In defining our hypotheses about independent variables (resilience factors), we focus on modifiable factors that can be targeted by prevention measures. Specifically, we hypothesize that social support, an increase in social support during the Corona crisis, optimism, general self-efficacy, good stress recovery, positive appraisal style (primary hypothesis), positive appraisal specifically of the Corona crisis, and behavioral coping are positively associated with resilience (outcome), while neuroticism is negatively associated with resilience. We also hypothesiz [...]
Background: Alzheimer's disease (AD) is the most common cause of dementia. Brain calcifications, ... more Background: Alzheimer's disease (AD) is the most common cause of dementia. Brain calcifications, as well as intracranial neoplasms, are also related with cognitive disorders. The association of these 3 conditions is very rare and to our knowledge not described yet. Objective: To describe a case of AD with a typical presentation associated with diffuse encephalic calcifications and a left frontal lobe meningeoma. Patient and Methods: A 79-year-old woman is reported. Diagnosis of AD was based on neurological examination, psychometric tests, neuroimaging findings, and exclusion of secondary dementia. She developed seizures at 9-year evolution of disease. A low thyroid stimulating hormone (TSH) level was detected and attributed to chronic use of amiodarone. Mini-Mental State Examination score was 7. Impaired verbal fluency and span digit test performance was observed. Severe perseveration and ecolalia were present. CT scan showed calcifications addressing cerebellum, basal ganglia, subcortical white matter, and occipital cortex. A meningeoma with left frontal lobe compression was also seen. Conclusion: Cognitive decline in AD may be in this case aggravated by simultaneous presence of other conditions such as diffuse encephalic calcifications and a frontal lobe meningeoma.
Anxiety reduction through mere expectation of anxiolytic treatment effects (placebo anxiolysis) h... more Anxiety reduction through mere expectation of anxiolytic treatment effects (placebo anxiolysis) has enormous clinical importance. Recent behavioral and electrophysiological data suggest that placebo anxiolysis involves reduced vigilance and enhanced internalization of attention; however, the underlying neurobiological mechanisms are not yet clear. Given the fundamental function of intrinsic connectivity networks (ICNs) in basic cognitive processes, we investigated ICN activity patterns associated with externally and internally directed mental states under the influence of an anxiolytic placebo medication. Based on recent findings, we specifically analyzed the functional role of the rostral anterior cingulate cortex (rACC) in coordinating placebo-dependent cue-related (phasic) and cue-unrelated (sustained) network activity. Under placebo, we observed a down-regulation of the entire salience network (SN), particularly in response to threatening cues. The rACC exhibited enhanced cue-unrelated functional connectivity (FC) with the SN, which correlated with reductions in tonic arousal and anxiety. Hence, apart from the frequently reported modulation of aversive cue responses, the rACC appears to be crucially involved in exerting a tonically dampening control over salience-responsive structures. In line with a more internally directed mental state, we also found enhanced FC within the default mode network (DMN), again predicting reductions in anxiety under placebo.
Neurorehabilitation and Neural Repair, Mar 16, 2007
To understand neural reorganization of response regulation after stroke, a 54-year-old woman with... more To understand neural reorganization of response regulation after stroke, a 54-year-old woman with a chronic left thalamic stroke performed a task requiring decisions about the directionality of an arrow during cerebral functional magnetic resonance imaging. Her performance was compared to 13 matched healthy control subjects. Her behavioral responses were slower but as accurate. Bilateral frontal activations were observed in the right medial frontal gyrus (BA 9), left superior frontal gyrus (BA 45), and left frontal rectus gyrus (BA 11). Activation in the right medial frontal gyrus, along with activity in close proximity to the anterior cingulate cortex, was observed, which may reflect reorganization of activity after the loss of function of the anterior cingulate cortex.
medRxiv (Cold Spring Harbor Laboratory), Aug 21, 2020
Deep learning approaches can uncover complex patterns in data. In particular, variational autoenc... more Deep learning approaches can uncover complex patterns in data. In particular, variational autoencoders (VAEs) achieve this by a non-linear mapping of data into a low-dimensional latent space. Motivated by an application to psychological resilience in the Mainz Resilience Project (MARP), which features intermittent longitudinal measurements of stressors and mental health, we propose an approach for individualized, dynamic modeling in this latent space. Specifically, we utilize ordinary differential equations (ODEs) and develop a novel technique for obtaining person-specific ODE parameters even in settings with a rather small number of individuals and observations, incomplete data, and a differing number of observations per individual. This technique allows us to subsequently investigate individual reactions to stimuli, such as the mental health impact of stressors. A potentially large number of baseline characteristics can then be linked to this individual response by regularized regression, e.g., for identifying resilience factors. Thus, our new method provides a way of connecting different kinds of complex longitudinal and baseline measures via individualized, dynamic models. The promising results obtained in the exemplary resilience application indicate that our proposal for dynamic deep learning might also be more generally useful for other application domains. NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
This fMRI study studied age-related differences in neural activities during response regulation. ... more This fMRI study studied age-related differences in neural activities during response regulation. Twenty-one male participants from two age groups, a younger group and an older group (mean ages: 29.9 and 65.2 years, respectively), were scanned while performing a task with response compatibility manipulation. They were presented with a sequence of arrowheads that pointed either upward or downward. In the "Response Compatible" condition, they were required to press an up or a down button consistent with the direction of the arrowhead. In the "Response Incompatible" condition, they were required to press the button opposite to the arrowhead direction so that an upward arrow should elicit a down response, and vice versa. Findings showed age-related differences in response regulation in several brain regions, including the right frontal, the right cingulate, and the left inferior parietal cortexes. The findings suggested a higher level of neural activity in the right prefrontal and left inferior parietal regions during response regulation for the older adults than for the younger adults.
Learning fear via the experience of contingencies between a conditioned stimulus (CS) and an aver... more Learning fear via the experience of contingencies between a conditioned stimulus (CS) and an aversive unconditioned stimulus (US) is often assumed to be fundamentally different from learning fear via instructions. An open question is whether fear-related brain areas respond differently to experienced CS-US contingencies than to merely instructed CS-US contingencies. Here, we contrasted two experimental conditions where subjects were instructed to expect the same CS-US contingencies while only one condition was characterized by prior experience with the CS-US contingency. Using multivoxel pattern analysis of fMRI data, we found CS-related neural activation patterns in the right amygdala (but not in other fear-related regions) that dissociated between whether a CS-US contingency had been instructed and experienced versus merely instructed. A second experiment further corroborated this finding by showing a categoryindependent neural response to instructed and experienced, but not merely instructed, CS presentations in the human right amygdala. Together, these findings are in line with previous studies showing that verbal fear instructions have a strong impact on both brain and behavior. However, even in the face of fear instructions, the human right amygdala still shows a separable neural pattern response to experience-based fear contingencies.
International Journal of Geriatric Psychiatry, Mar 1, 2004
Memory difficulty is one of the most common complaints of older people, with or without psychiatr... more Memory difficulty is one of the most common complaints of older people, with or without psychiatric conditions. It is therefore of utmost important to understand how normal ageing process impacts upon prose memory so as to gain insight into ways to differentiate pathological vs normal age-related changes of the recall of prose observed among older people. To understand the differential age-related change of prose memory in older Hong Kong Chinese of higher and lower education. Forty-eight normal, healthy Cantonese-speaking Chinese were recruited. Seventeen of them were younger, highly educated participants. Among the 31 older people recruited, 19 of them received education comparable with the younger participants and 12 were older people of low education. A prose passage was constructed to measure the different processes of prose memory, including learning efficiency, rate of forgetting, recall accuracy, accuracy of temporal sequence of information recalled, distortions, and recognition memory. As expected, ageing affected all the processes of prose memory measured, except the rate of forgetting. Apart from learning efficiency and rate of forgetting, education was observed to modify the effect of ageing on all the processes studied. Changes of prose memory associated with ageing and the differential effect of education on prose recall among older people were discussed. The findings seem to suggest that prose memory is a multifaceted construct.
Motivated by the recent replicability crisis we tested replicability of functional magnetic reson... more Motivated by the recent replicability crisis we tested replicability of functional magnetic resonance imaging (fMRI) group activations in two independent samples. An identical behavioral and fMRI test battery for the longitudinal investigation of stress resilience mechanisms was developed for the Mainz Resilience Project (MARP) and conducted in a discovery (N ¼ 54) and a replication sample (N ¼ 103). The test battery consisted of a stress reactivity task, a reward sensitivity task, a fear conditioning and extinction paradigm, two volitional reappraisal tasks and an emotional interference inhibition task. Replicability of group activations was tested with the Jaccard index and the Intra Class Correlation (ICC). Overall, we observed good to excellent replicability of activations at the whole brain level. Only a minority of contrasts showed unsatisfactory replicability. Replicability at the level of individual regions of interest (ROIs) was generally lower. Tasks with stronger activation in the discovery sample showed better replicability.
BACKGROUND Stress-related mental disorders are highly prevalent and pose a substantial burden on ... more BACKGROUND Stress-related mental disorders are highly prevalent and pose a substantial burden on individuals and society. Improving strategies for the prevention and treatment of mental disorders requires a better understanding of their risk and resilience factors. This multicenter study aims to contribute to this endeavor by investigating psychological resilience in healthy but susceptible young adults over 9 months. Resilience is conceptualized in this study as the maintenance of mental health or quick recovery from mental health perturbations upon exposure to stressors, assessed longitudinally via frequent monitoring of stressors and mental health. OBJECTIVE This study aims to investigate the factors predicting mental resilience and adaptive processes and mechanisms contributing to mental resilience and to provide a methodological and evidence-based framework for later intervention studies. METHODS In a multicenter setting, across 5 research sites, a sample with a total target size of 250 young male and female adults was assessed longitudinally over 9 months. Participants were included if they reported at least 3 past stressful life events and an elevated level of (internalizing) mental health problems but were not presently affected by any mental disorder other than mild depression. At baseline, sociodemographic, psychological, neuropsychological, structural, and functional brain imaging; salivary cortisol and α-amylase levels; and cardiovascular data were acquired. In a 6-month longitudinal phase 1, stressor exposure, mental health problems, and perceived positive appraisal were monitored biweekly in a web-based environment, while ecological momentary assessments and ecological physiological assessments took place once per month for 1 week, using mobile phones and wristbands. In a subsequent 3-month longitudinal phase 2, web-based monitoring was reduced to once a month, and psychological resilience and risk factors were assessed again at the end of the 9-month period. In addition, samples for genetic, epigenetic, and microbiome analyses were collected at baseline and at months 3 and 6. As an approximation of resilience, an individual stressor reactivity score will be calculated. Using regularized regression methods, network modeling, ordinary differential equations, landmarking methods, and neural net–based methods for imputation and dimension reduction, we will identify the predictors and mechanisms of stressor reactivity and thus be able to identify resilience factors and mechanisms that facilitate adaptation to stressors. RESULTS Participant inclusion began in October 2020, and data acquisition was completed in June 2022. A total of 249 participants were assessed at baseline, 209 finished longitudinal phase 1, and 153 finished longitudinal phase 2. CONCLUSIONS The Dynamic Modelling of Resilience–Observational Study provides a methodological framework and data set to identify predictors and mechanisms of mental resilience, which are intended to serve as an empirical foundation for future intervention studies. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/39817
Background: The rising prevalence of stress-related mental and physical disorders over the past d... more Background: The rising prevalence of stress-related mental and physical disorders over the past decades, and more recently in connection to the COVID-19 pandemic, highlights the need for a better understanding of stress-protective factors (resilience factors) Resilience has been conceptualised as the maintenance or quick recovery of mental health following exposure to adversity By studying psycho-social factors that influence resilience in the context of the COVID-19 pandemic, it was possible to examine population-wide responses to stressors of unusually similar nature Methods: In a first interim analysis of an international resilience study we examined data from 5000 European adults collected during the first phases of pandemic-related movement and contact restrictions (‘lockdown’) Linear regression, regularised regression, and mediation analyses were employed to compare the influence of nine potential resilience factors according to preregistered hypotheses (osf io/r6btn) Results: All hypothesized resilience factors were significantly associated with resilience as an outcome Compared to other resilience factors, positive appraisal of the COVID-19 pandemic showed the strongest effect Results confirmed our primary hypothesis that general positive appraisal style (PAS) is positively associated with resilience, and further revealed that PAS mediates the positive influence of perceived social support on resilience Discussion: The investigated resilience factors provide promising targets for health interventions that aim to improve stress resilience in general or in the face of prolonged pandemic-related adversity To improve intervention planning, future research should also investigate the influence of socio-demographic factors on resilience factor use and efficacy, as well as the dynamics of time-variant resilience development in response to stressors exposure
bioRxiv (Cold Spring Harbor Laboratory), Nov 17, 2018
Resilience is the maintenance or rapid recovery of mental health during and after stressor exposu... more Resilience is the maintenance or rapid recovery of mental health during and after stressor exposure. It is becoming increasingly clear that resilience results from a complex and dynamic process of adaptation to stressors involving the biological, psychological and social levels. Positive appraisal style theory of resilience (PASTOR) claims that the common final pathway to maintained mental health lies in the non-negative (non-catastrophizing, nonpessimistic) appraisal of potential stressors, permitting the organism to fine-tune stress responses to optimal levels, thus avoiding unnecessary stress, inefficient deployment of resources and concomitant deleterious allostatic load effects. Successful adaptation consists in developing or strengthening a positive appraisal style. Another key element of PASTOR is that a positive appraisal style is strongly determined by the efficacy and efficiency of the neural and cognitive processes that underlie positive stressor appraisal. We here present a combined behavioral and functional magnetic resonance imaging (fMRI) battery designed to assess such processes repeatedly in longitudinal settings. The battery includes tests of stress reactivity and recovery, reward sensitivity, safety learning and memory in the context of fear conditioning and extinction, volitional situation-focused reappraisal, volitional self-focused reappraisal, and emotional interference inhibition, along with structural MRI and resting-state MRI scans. A detailed description of the battery methods is provided. The feasibility of the battery was successfully tested in N=55 healthy subjects; group results of the individual tasks largely replicate existing literature.
Dopamine dysfunction is associated with a wide range of neuropsychiatric disorders commonly treat... more Dopamine dysfunction is associated with a wide range of neuropsychiatric disorders commonly treated pharmacologically or invasively. Recent studies provide evidence for a nonpharmacological and noninvasive alternative that allows similar manipulation of the dopaminergic system: transcranial direct current stimulation (tDCS). In rodents, tDCS has been shown to increase neural activity in subcortical parts of the dopaminergic system, and recent studies in humans provide evidence that tDCS over prefrontal regions induces striatal dopamine release and affects reward-related behavior. Based on these findings, we used fMRI in healthy human participants and measured the fractional amplitude of low-frequency fluctuations to assess spontaneous neural activity strength in regions of the mesostriatal dopamine system before and after tDCS over prefrontal regions (n ϭ 40, 22 females). In a second study, we examined the effect of a single dose of the dopamine precursor levodopa (L-DOPA) on mesostriatal fractional amplitude of low-frequency fluctuation values in male humans (n ϭ 22) and compared the results between both studies. We found that prefrontal tDCS and L-DOPA both enhance neural activity in core regions of the dopaminergic system and show similar subcortical activation patterns. We furthermore assessed the spatial similarity of whole-brain statistical parametric maps, indicating tDCS-andL-DOPA-inducedactivation,andϾ100neuronalreceptorgeneexpressionmapsbasedontranscriptionaldatafromtheAllenInstitute forBrainScience.Inlinewithaspecificactivationofthedopaminergicsystem,wefoundthatbothinterventionspredominantlyactivatedregions with high expression levels of the dopamine receptors D2 and D3.
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Papers by Kenneth Yuen