Alexandra Sebastian

Stress resilience is the maintenance of mental health despite adversity. We have predicted that a tendency to appraise stressors in a realistic to slightly unrealistically positive fashion (positive appraisal style, PAS) is prospectively associated with more resilient outcomes; that PAS is a proximal and integrative resilience factor, mediating the pro-resilience effects of other protective factors (e.g., social support); and that PAS is modifiable, with changes in PAS leading to corresponding changes in resilience. In two independent observational samples (N=132 and N=1034), we find PAS to predict resilience over three and more years and to mediate the positive effects of social support. Analyzing the effects of a multi-component intervention (N=232) that targets a broad set of resilience factors, we find that the intervention increases PAS and that this prospectively mediates the intervention-induced increases in resilience. This establishes PAS as a proximal and plastic resilience factor with likely causal effects on resilience.

The estimated latency of the unobservable stop response, the so-called stop-signal reaction time (SSRT), has been the established measure of performance in the stop-signal task. While it is currently debated whether SSRT is a suitable marker of inhibition performance, other markers such as the reliability of triggering the stop process (“stop trigger failures”) are coming into focus. In the present study, we elucidated the mechanisms associated with trigger failures using a model-based neuroscience approach by means of functional magnetic resonance imaging for the first time. To this end, we used a large, open-access fMRI data set to investigate the relationship between the probability of trigger failures and fMRI signal change in a stop-signal task in healthy adults (n = 113). Stop trigger failures were associated with less activity in the substantia nigra during unsuccessful stopping and with less activity in the subthalamic nucleus (STN) region during successful inhibition. Although stop trigger failures strongly correlated with SSRT, we found only little evidence for a correlation between SSRT and stopping-related fMRI signal. Thus, in particular, the reliability of the stop process and not its estimated latency depends on the recruitment of key nodes within the prefrontal-subthalamic hyperdirect pathway. More specifically, stop trigger failures may be linked to inadequate substantia nigra innervation at the neural network level. As current evidence suggests that the hyperdirect pathway is engaged by the processing of salient stimuli, deficiencies in assessing the relevance of the stop signal may represent a phenotype associated with a propensity to trigger the stop process unreliably.

Appraisal refers to the evaluation of stimuli or situations with respect to an individual’s goals and needs. Stimuli or situations that are appraised as a threat to one’ goals and needs (‘stressors’) induce stress responses (‘stress’). Stressor appraisal occurs on various dimensions, of which the magnitude or cost of a potential adverse outcome, the probability of the outcome, and an individual’s coping potential are the most important. Individuals show subjective biases on each of these dimensions, which can range from extremely unrealistically negative to extremely unrealistically positive. Positive appraisal style (PAS) is an integrative construct. Individuals with a PAS have an average tendency to appraise stressors in a realistic to mildly unrealistically positive fashion across the different stressor appraisal dimensions; hence, they typically avoid both negative and also delusionally positive appraisals. Positive appraisal style theory of resilience (PASTOR) posits that this global bias is key for stress resilience, as it enables individuals to generate stress responses when needed but also to avoid unnecessary and over-shooting stress responses that will exhaust one’s resources and prevent resource replenishment during times of severe or lasting stressor exposure. We here use data from three prospective-longitudinal studies to compare recently validated self-report instruments for PAS with existing measures of appraisal biases in single dimensions in their relative predictive potential for resilience, using regularized regression methodology. We find that one PAS instrument, reflecting a tendency to produce general positive appraisal contents (PASS-content), and an optimism instrument, supposed to reflect a positive appraisal bias on the probability dimension, are consistent predictors of resilience over long time frames and superior in this quality to the other instruments (measures of positive appraisal processes, self-efficacy, and control). Generally, our results confirm the important role of appraisal biases in resilience. Item and nomological network analyses further indicate that the PASS-content instrument may more closely reflect individual differences in appraisal than the optimism instrument and thus be well suited for mechanistically interpretable prediction models based on well-defined psychological constructs. By contrast, the optimism instrument may reflect differences in life perspectives in addition to differences in appraisal. This makes the instrument less mechanistically interpretable; however, it may be better suited for clinical prediction models aiming at individual-level prognosis on the basis of maximized explained variance.

Highly arousing, affective stimuli have adverse effects on cognition and performance. Perception of affective stimuli is, however, highly subjective and may impact on the interaction of emotion and cognition. Here, we tested the impact of high- versus low-threatening stimuli on response inhibition as a function of perceived threat intensity. Response inhibition was probed using a stop-signal paradigm in 62 healthy adults. We used stop-signals that had previously been paired with an unpleasant electrodermal stimulation (i.e., high-threat stimuli) or that had never been paired with electrodermal stimulation (i.e., low-threat stimuli). High-threat stimuli did not affect stopping performance in general. Only participants who perceived the high-threat stimuli as highly painful showed impaired response inhibition on high-threat trials relative to low-threat trials. Participants who perceived the high-threat as mildly painful, however, showed improved response inhibition on high-threat trials. This effect was not moderated by the current anxious state. This suggests that the impact of negative affective stimuli on cognition critically depends on subjective threat perception. Ratings of affective stimuli should be included in studies probing the emotion-cognition interaction because subjective perception might strongly impact on that interaction. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Motor inhibitory control implemented as response inhibition is an essential cognitive function required to dynamically adapt to rapidly changing environments. Despite over a decade of research on the neural mechanisms of response inhibition, it remains unclear, how exactly response inhibition is initiated and implemented. Using a multimodal MEG/fMRI approach in 59 subjects, our results reliably reveal that response inhibition is initiated by the right inferior frontal gyrus (rIFG) as a form of attention-independent top-down control that involves the modulation of beta-band activity. Furthermore, stopping performance was predicted by beta-band power, and beta-band connectivity was directed from rIFG to pre-supplementary motor area (pre-SMA), indicating rIFG’s dominance over pre-SMA. Thus, these results strongly support the hypothesis that rIFG initiates stopping, implemented by beta-band oscillations with potential to open up new ways of spatially localized oscillation-based interventions.

Unexpected and thus surprising events are omnipresent and oftentimes require adaptive behavior such as unexpected inhibition or unexpected action. The current theory of unexpected events suggests that such unexpected events just like global stopping recruit a fronto-basal-ganglia network. A global suppressive effect impacting ongoing motor responses and cognition is specifically attributed to the subthalamic nucleus (STN). Previous studies either used separate tasks or presented unexpected, task-unrelated stimuli during response inhibition tasks to relate the neural signature of unexpected events to that of stopping. Here, we aimed to test these predictions using a within task design with identical stimulus material for both unexpected action and unexpected inhibition using functional magnetic resonance imaging (fMRI) for the first time. To this end, 32 healthy human participants of both sexes performed a cue-informed go/nogo task comprising expected and unexpected action and inhibition trials during fMRI. Using conjunction, contrast, and Bayesian analyses, we demonstrate that unexpected action elicited by an unexpected go signal and unexpected inhibition elicited by an unexpected nogo signal recruited the same fronto-basal-ganglia network which is usually assigned to stopping. Furthermore, the stronger the unexpected action-related activity in the STN region was the more detrimental was the effect on response times. The present results thus complement earlier findings and provide direct evidence for the unified theory of unexpected events while ruling out alternative task and novelty effects.SIGNIFICANCE STATEMENTThis is the first study using functional magnetic resonance imaging (fMRI) to test whether unexpected events regardless of whether they require unexpected action or inhibition recruit a fronto-basal-ganglia network just like stopping. In contrast to previous studies, we used identical stimulus material for both conditions within one task. This enabled us to directly test predictions of the current theory of unexpected events and, moreover, to test for condition-specific neural signatures. The present results underpin that both processes recruit the same neural network while excluding alternative task and novelty effects. The simple task design thus provides an avenue to studying surprise as a pure form of reactive inhibition in neuropsychiatric patients displaying inhibitory deficits who often have a limited testing capacity.

Summary: Both the right inferior frontal gyrus (rIFG) and the pre-supplementary motor area (pre-SMA) are crucial for successful response inhibition. However, the particular functional roles of those two regions have been controversially debated for more than a decade now. It is unclear whether the rIFG directly initiates stopping or serves an attentional function, whereas the stopping is triggered by the pre-SMA. The current multimodal MEG/fMRI study sought to clarify the role and temporal activation order of both regions in response inhibition using a selective stopping task. This task dissociates inhibitory from attentional processes. Our results reliably reveal a temporal precedence of rIFG over pre-SMA. Moreover, connectivity during response inhibition is directed from rIFG to pre-SMA and predicts stopping performance. Response inhibition is implemented via beta-band oscillations. Our findings support the hypothesis that response inhibition is initiated by the rIFG as a form of attention-independent top-down control.

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, non-pessimistic) 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.