Individual differences in resilience to stress are associated with affective flexibility

Cognitive flexibility, the capacity to adjust behavior to changing situational demands, is frequently linked to resilience because of its important contribution to stress regulation. In this context, particularly affective flexibility, defined as the ability to flexibly attend and disengage from affective information, may play a significant role. However, there are so far only very few empirical investigations that directly explore the link between flexibility and resilience to stress. In the present study, the relationship of cognitive and affective flexibility and resilience was examined in 100 healthy participants. Resilience was measured with three self-report questionnaires, two defining resilience as a personality trait and one focusing on resilience as an outcome in the sense of stress coping abilities. Cognitive and affective flexibility were assessed in two experimental task switching paradigms with non-affective and affective materials and tasks, respectively. The cognitive flexibility paradigm additionally included measures of cognitive stability and dispositional cognitive flexibility. In the affective flexibility paradigm, we explicitly considered the affective valence of the stimuli before and during task switching. Response time switch costs in the affective flexibility paradigm were significantly correlated to all three self-report measures of resilience. Regarding the valence of the stimuli, the correlation with resilience was not specific to costs when switching from negative to positive information or vice versa. For cognitive (i.e., non-affective) flexibility, a significant correlation of response time switch costs was found with only one of the three resilience measures. A regression analysis including both affective and cognitive switch costs as predictors of resilience indicated that only affective, but not cognitive switch costs, explained unique variance components. Furthermore, the experimental measures of cognitive stability and dispositional cognitive flexibility did not correlate with resilience scores. These findings suggest that specifically the efficiency of flexibly switching between affective and non-affective information is related to resilience.

No need to choose: independent regulation of cognitive stability and flexibility challenges the stability-flexibility tradeoff

Adaptive behavior requires the ability to focus on a current task and protect it from distraction (cognitive stability) as well as the ability to rapidly switch to another task in light of changing circumstances (cognitive flexibility). Cognitive stability and flexibility have commonly been conceptualized as opposite endpoints on a stability-flexibility tradeoff continuum, implying an obligatory reciprocity between the two: greater flexibility necessitates less stability, and vice versa. Surprisingly, rigorous empirical tests of this critical assumption are lacking, however. Here, we tested this assumption by acquiring simultaneous measurements of cognitive stability (congruency effects) and flexibility (switch costs) while independently varying contextual demands on these functions with block-wise manipulations of the proportion of incongruent trials and task switches, respectively. If cognitive stability and flexibility are reciprocal, an increase in flexibility in response to higher switch rates should lead to a commensurate decrease in stability, and an increase in stability in response to more frequent incongruent trials should result in decreased flexibility. Across three experiments, using classic cued task switching (Experiments 1 and 3) and attentional set shifting (Experiment 2) protocols, we found robust evidence against an obligatory stability-flexibility tradeoff. Although we observed the expected contextual adaptation of stability and flexibility to changing demands, strategic adjustments in stability had no influence on flexibility, and vice versa. These results refute the long-held assumption of a stability-flexibility tradeoff, documenting instead that the cognitive processes mediating these functions can be regulated independently - it is possible to be both stable and flexible at the same time.

Stronger Educational Performance in Early Life Correlates with Higher Cancer Risk, Lower Dementia Risk and Lower All-cause Mortality in Later Life – but Why?

Better functioning nervous system stimulates other organs, promoting longevity. As a trade-off, this stimulation may result in enhanced oncogenesis. This hypothesis was tested by analyzing factors reflecting cognitive score and academic performance, Educational performance emerged as a universal independent negative correlate for most of comorbidities, except cancer, that forms a positive correlate. More educated individuals demonstrate more aggressive neoplasia and cancer patients demonstrate lesser mental and physical decline as compared with controls. Cognitive stability and high cognitive score were the statistically strongest anti-correlates of all-cause mortality, pointing to neurological health as the principal mediator of survival. The patients remaining clinically normal despite decreased cognitive scores demonstrated anomalously low mortality (~2.5% annual in the 90 years old). Such “dementia resister” phenotype was more prevalent in the higher education cohorts, which also demonstrated a delayed aging rate. Remaining life expectancy was linearly proportional to the baseline cognitive score. We proposed that systemic non-trauma mobilization of stem-cell activity by CNS acts as a permanent regenerative endogenous factor with the trade-off of increased cancer risk due to similar interactions with cancer stem cells. Novel markers of mortality risk can follow as practical applications.

Optimal ATN biomarkers and their role in predicting cognitive progress of mild cognitive impairment

Background It is of great significance to investigate the optimal cerebrospinal fluid (CSF) and magnetic resonance image biomarkers of ATN system and clarify their predictive value in cognitive progression of mild cognitive impairment individuals (MCI). Methods 147 healthy control (HC), 197 patients with MCI, and 128 patients with Alzheimer’ Disease (AD) were included from the ADNI database. All MCI patients were followed up from 6 to 60 months. The amyloid (A) was assessed by CSF Aβ42 or Aβ42/Aβ40. The tau pathology (T) was assessed by CSF p-tau. The neurodegeneration (N) was assessed by radiomics of the whole brain MRI or by CSF t-tau. Biomarkers with larger area under the receiver operating characteristic curve (AUC) in the discrimination of AD and HC were considered to be the optimal biomarkers. The conversion rates of different ATN profiles in MCI subjects during follow-up were analyzed using Kaplan-Meier estimates and compared using the Log-rank test. Results The CSF Aβ 42 and the radiomics signature (AUC 0.822 and 0.998, respectively) were identified as the optimal A and N biomarkers, respectively. For MCI patients of the Alzheimer continuum, there was no significant difference in the progression rate of A + T − N− and A − T−N − profiles (p > 0.05). The A + T + N−, A + T − N + profiles had a significant higher progression rate than that of the A + T − N− patients (all p < 0.05). For MCI of the suspected non-AD pathophysiology (SNAP), patients with the A − T−N + profile (p < 0.05) showed significant higher progression rate than A − T−N − profile. There was no significant difference in the progression rate of A − T + N − and A − T−N − profiles (p > 0.05). Discussion We proposed a new radiomics method to assess N accurately and ascertained the optimal A/T/N biomarkers for the discrimination of HC and AD. For MCI patients of the Alzheimer continuum, isolated A + was indicator of cognitive stability, while the abnormality of T and N, respectively or simultaneously, indicated the high risk of progression. For MCI patients of SNAP, isolated T + indicated the cognitive stability, while the appearance of N + indicated the high risk of progression.

Rationalizing Constraints on the Capacity for Cognitive Control

Humans are remarkably limited in (a) how many control-dependent tasks they can execute simultaneously, and (b) how intensely they can focus on a single task. These limitations are universal assumptions of most theories of cognition. Yet, a rationale for why humans are subject to these constraints remains elusive. This review draws on recent insights from psychology, neuroscience and machine learning, to suggest that constraints on cognitive control may result from a rational adaptation to fundamental computational dilemmas in neural architectures. The reviewed literature implies that limitations in multitasking may result from a tradeoff between learning efficacy and processing efficiency, and that limitations in the intensity of commitment to a single task may reflect a tradeoff between cognitive stability and flexibility.

To stay or not to stay: The stability of choice perseveration in value-based decision making

In real life, decisions are often naturally embedded in decision sequences. In contrast, in the laboratory, decisions are oftentimes analysed in isolation. Here, we investigated the influence of decision sequences in value-based decision making and whether the stability of such effects can be modulated. In our decision task, participants needed to collect rewards in a virtual two-dimensional world. We presented a series of two reward options that were either quick to collect but were smaller in value or took longer to collect but were larger in value. The subjective value of each option was driven by the options’ value and how quickly they could be reached. We manipulated the subjective values of the options so that one option became gradually less valuable over the course of a sequence, which allowed us to measure choice perseveration (i.e., how long participants stick to this option). In two experiments, we further manipulated the time interval between two trials (inter-trial interval), and the time delay between the onsets of both reward options (stimulus onset asynchrony). We predicted how these manipulations would affect choice perseveration using a computational attractor model. Our results indicate that both the inter-trial interval and the stimulus onset asynchrony modulate choice perseveration as predicted by the model. We discuss how our findings extend to research on cognitive stability and flexibility.

How Sequentially Changing Reward Prospect Modulates Meta-control: Increasing Reward Prospect Promotes Cognitive Flexibility

Meta-control is necessary to regulate the balance between cognitive stability and flexibility. Evidence from (voluntary) task switching studies suggests performance-contingent reward as one modulating factor. Depending on the immediate reward history, reward prospect seems to promote either cognitive stability or flexibility: Increasing reward prospect reduced switch costs and increased the voluntary switch rate, suggesting increased cognitive flexibility. In contrast, remaining high reward prospect increased switch costs and reduced the voluntary switch rate, suggesting increased cognitive stability. Recently we suggested that increasing reward prospect serves as a meta-control signal toward cognitive flexibility by lowering the updating threshold in working memory. However, in task switching paradigms with two tasks only, this could alternatively be explained by facilitated switching to the other of two tasks. To address this issue, a series of task switching experiments with uncued task switching between three univalent tasks was conducted. Results showed a reduction in reaction time (RT) switch costs to a nonsignificant difference and a high voluntary switch rate when reward prospect increased, whereas repetition RTs were faster, switch RTs slower, and voluntary switch rate was reduced when reward prospect remained high. That is, increasing reward prospect put participants in a state of equal readiness to respond to any target stimulus—be it a task repetition or a switch to one of the other two tasks. The study thus provides further evidence for the assumption that increasing reward prospect serves as a meta-control signal to increase cognitive flexibility, presumably by lowering the updating threshold in working memory.

T136. NEURAL CORRELATES OF ALTERED COGNITIVE FLEXIBILITY AND STABILITY FOR MOTOR CONTROL IN SCHIZOPHRENIA – JUST TWO SIDES OF THE SAME COIN?

Background It has been suggested that patients with schizophrenia are impaired in the use of prediction error signals resulting in disturbances of motor control. Alterations in fronto-striatal dopamine transmitter systems are regarded to contribute to these deficits. It is unclear whether the use of predictive strategies for motor control may be systematically related to impaired cognitive functions in patients. In healthy subjects, cognitive flexibility has been related to medial prefrontal cortex (PFC) function, while cognitive stability was related to lateral PFC integrity with both brain regions being modulated by striatal activity. Despite these findings, the interplay of cognitive flexibility and stability needed for motor control and its associations to alterations on the brain system level have not been investigated systematically in this patient group. Methods We assessed patients with schizophrenia (N=22) and healthy controls (N=22) on first, detection of relevant unexpected events (cognitive flexibility) and second, distractor resistance to irrelevant prediction errors (cognitive stability) using a serial prediction task including the digits 1-2-3-4. We applied an event-related design in a functional magnetic resonance imaging (fMRI) environment (3T) to explore brain networks underlying cognitive flexibility and stability, respectively. In analyses, the minimum cluster extent was set to k &gt; 20 and corrected using the false discovery rate (FDR) with p &lt; 0.05. Since we were specifically interested in the role of the striatum, we applied small volume correction at p &lt; 0.05 with the minimum cluster extent set to k &gt; 5 in a region of interest analyses. Participants were also assessed on general cognitive function using the Brief Assessment of Cognition in Schizophrenia (BACS) battery and on motor symptoms using the Heidelberg Scale for Neurological Soft Signs (NSS). Results Patients detected less behaviorally relevant events (M(Pat) = 0.57 vs. M(HC) = 0.78, F(41,1) = 16.32, p &lt; 0.001) and ignored less irrelevant events (M(Pat) = 0.87 vs. M(HC) = 0.93, F(41,1) = 11.78, p &lt; 0.001) implying impairments of both cognitive flexibility and stability in patients. Motor symptoms (NSS) and cognitive deficits (BACS) in patients were exclusively related to cognitive flexibility, but not stability. Brain correlates of reduced flexibility in patients were found in a fronto-striato-thalamo network. More specifically, reduced striatal activation in patients was related to weaker event discrimination and reduced detection of unexpected relevant events. Additionally, exploratory follow-up analyses revealed reduced fronto-striato-temporal activation in patients associated with weaker distractor resistance during the stability task. Note, chlorpromazine equivalents as an indicator of antipsychotic dosage as well as positive and negative symptoms were unrelated to measures of cognitive flexibility and stability. Discussion Together, our findings provide evidence for distinctive neurobiological alterations underlying reduced cognitive flexibility and stability in schizophrenia with reduced flexibility being associated with general cognitive and motor impairments. Our main imaging results show reduced activation in a fronto-striato-thalamo network in response to relevant prediction errors in patients, while impaired cognitive stability may be rather related to alterations in a fronto-striato-temporal network. Reduced caudate activation during behavioral relevant events, which was associated with weaker event discrimination and detection of relevant prediction errors in patients, supports a model of striatal gating being essentially impaired in patients.

Increased dopamine availability magnifies nicotine effects on cognitive control: A pilot study

Introduction and objectives: The ability to adapt to new task demands flexibly and to stabilise performance in the presence of distractors is termed cognitive control and is mediated by dopaminergic and cholinergic neurotransmission. We aimed to test the hypothesis that the effect of the cholinergic agonist nicotine on cognitive control depends on baseline dopamine levels. Methods: Thirty-eight healthy non-smokers (16 males; Mage=24.05 years) performed a cognitive control task including distractor and switch trials twice. Subjects were split into two parallel groups. One group received 2 g of L-tyrosine two hours prior to testing to manipulate dopamine availability experimentally, while the other group received placebo on both days. One hour later, both groups received in a within-subject design: on one day, a 7 mg nicotine patch; on the other day, a matched placebo. Response time costs for distractor and switch trials served as measures of cognitive stability and flexibility. Results: Nicotinic modulation reduced response time costs in switch trials and increased costs in distractor trials (nicotine×condition, p=0.027) with a trend-wise interaction between nicotine, L-tyrosine and trial type (nicotine×L-tyrosine×condition, p=0.068), which was due to stronger nicotine effects under L-tyrosine. Conclusions: Our data provide preliminary evidence that nicotine has opponent effects on cognitive stability and flexibility. Subjects who received the dopamine precursor L-tyrosine were more prone to nicotine effects on behaviours, which are improvements in cognitive flexibility at the cost of decreased cognitive stability.