Spatial biases during mental arithmetic: evidence from eye movements on a blank screen

While the influence of spatial-numerical associations in number categorization tasks has been well established, their role in mental arithmetic is less clear. It has been hypothesized that mental addition leads to rightward and upward shifts of spatial attention (along the “mental number line”), whereas subtraction leads to leftward and downward shifts. We addressed this hypothesis by analyzing spontaneous eye movements during mental arithmetic. Participants solved verbally presented arithmetic problems (e.g., 2 + 7, 8–3) aloud while looking at a blank screen. We found that eye movements reflected spatial biases in the ongoing mental operation: Gaze position shifted more upward when participants solved addition compared to subtraction problems, and the horizontal gaze position was partly determined by the magnitude of the operands. Interestingly, the difference between addition and subtraction trials was driven by the operator (plus vs. minus) but was not influenced by the computational process. Thus, our results do not support the idea of a mental movement toward the solution during arithmetic but indicate a semantic association between operation and space.

Delayed response and lack of habituation in plasma interleukin-6 to acute mental stress in men

Acute mental stress induces a significant increase in plasma interleukin (IL)-6 levels as a possible mechanism for how psychological stress might contribute to atherosclerosis. We investigated whether the IL-6 response would habituate in response to a repetitively applied mental stressor and whether cortisol reactivity would show a relationship with IL-6 reactivity. Study participants were 21 reasonably healthy men (mean age 46+/-7 years) who underwent the Trier Social Stress Test (combination of a 3-min preparation, 5-min speech, and 5-min mental arithmetic) three times with an interval of 1 week. Plasma IL-6 and free salivary cortisol were measured immediately before and after stress, and at 45 and 105 min of recovery from stress. Cortisol samples were also obtained 15 and 30 min after stress. Compared to non-stressed controls, IL-6 significantly increased between rest and 45 min post-stress (p=.022) and between rest and 105 min post-stress (p=.001). Peak cortisol (p=.034) and systolic blood pressure (p=.009) responses to stress both habituated between weeks one and three. No adaptation occurred in diastolic blood pressure, heart rate, and IL-6 responses to stress. The areas under the curve integrating the stress-induced changes in cortisol and IL-6 reactivity were negatively correlated at visit three (r=-.54, p=.011), but not at visit one. The IL-6 response to acute mental stress occurs delayed and shows no adaptation to repeated moderate mental stress. The hypothalamus-pituitary-adrenal axis may attenuate stress reactivity of IL-6. The lack of habituation in IL-6 responses to daily stress could subject at-risk individuals to higher atherosclerotic morbidity and mortality.

Low social support and poor emotional regulation are associated with increased stress hormone reactivity to mental stress in systemic hypertension

CONTEXT: There is strong evidence for a physiological hyperreactivity to stress in systemic hypertension, but data on associated or potentially moderating psychological factors are scarce. OBJECTIVE: The objective of the study was to identify psychological correlates of physiological stress reactivity in systemic hypertension. DESIGN: This was a cross-sectional, quasi-experimentally controlled study. Study participants underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. SETTING: The study was conducted in the population in the state of Zurich, Switzerland. SUBJECTS: Subjects included 22 hypertensive and 26 normotensive men (mean +/- sem 44 +/- 2 yr). MAIN OUTCOME MEASURES: We assessed the psychological measures social support, emotional regulation, and cognitive appraisal of the stressful situation. Moreover, we measured salivary cortisol and plasma epinephrine and norepinephrine before and after stress and several times up to 60 min thereafter as well as blood pressure and heart rate. RESULTS: We found poorer hedonistic emotional regulation (HER) and lower perceived social support in hypertensives, compared with normotensives (P < 0.01). Compared with normotensives, hypertensives showed higher cortisol, epinephrine, and norepinephrine secretions after stress (P < 0.038) as well as higher systolic and diastolic blood pressure (P < 0.001). Cortisol reactivity and norepinephrine secretion were highest in hypertensive men with low HER (P < 0.05). In contrast, hypertensives with high HER did not significantly differ from normotensives in both cortisol and norepinephrine secretion after stress. Epinephrine secretion was highest in hypertensives with low social support but was not different between hypertensives with high social support and normotensives. CONCLUSIONS: The findings suggest that both low social support and low HER are associated with elevated stress hormone reactivity in systemic hypertension.

The effect of natural habituation on coagulation responses to acute mental stress and recovery in men

Blood coagulation activation might be one mechanism linking acute mental stress with coronary events. We investigated the natural habituation of coagulation responses and recovery to short-term mental stress. Three times with one-week intervals, 24 men (mean age 47 +/- 7 years) underwent the same 13-min stressor (preparation, job interview, mental arithmetic). During each visit venous blood was obtained four times (baseline, immediately post-stress, 45 min of recovery, 105 min of recovery). Eight blood coagulation parameters were measured at weeks one and three. Acute stress provoked increases in von Willebrand factor antigen, fibrinogen, clotting factor FVII activity (FVII:C), FVIII:C, FXII:C (p's < or = 0.019), and D-dimer (N.S.). All coagulation parameters experienced full recovery except FVIII:C (p = 0.022). Stress did not significantly affect activated partial thromboplastin time and prothrombin time. At all time points FVIII:C and FXII:C levels were significantly higher at week one compared to week three (p's < or = 0.041). Before catheter insertion, systolic blood pressure (p = 0.001) and heart rate (p = 0.026) were relatively higher at week one. Unlike the magnitude of systolic blood pressure response to stress (p = 0.007) and of cortisol recovery from stress (p = 0.002), the magnitude of all coagulation responses to stress and the recovery from stress were similar in week one and week three. Sympathetic activation with anticipatory stress best explained increased baseline activity in FVIII and FXII at week one. An incapacity of the coagulation system to adapt to stress repeats is perhaps a consequence of evolution, but might also contribute to increased coronary risk in some individuals, particularly in those with cardiovascular diseases.

Sleep restriction attenuates amplitudes and attentional modulation of pain-related evoked potentials, but augments pain ratings in healthy volunteers

The experiment investigated the impact of sleep restriction on pain perception and related evoked potential correlates (laser-evoked potentials, LEPs). Ten healthy subjects with good sleep quality were investigated in the morning twice, once after habitual sleep and once after partial sleep restriction. Additionally, we studied the impact of attentional focussing on pain and LEPs by directing attention to (intensity discrimination) or away from the stimulus (mental arithmetic). Laser stimuli directed to the hand dorsum were rated as 30% more painful after sleep restriction (49+/-7 mm) than after a night of habitual sleep (38+/-7 mm). A significant interaction between attentional focus and sleep condition suggested that attentional focusing was less distinctive under sleep restriction. Intensity discrimination was preserved. In contrast, the amplitude of the early parasylvian N1 of LEPs was significantly smaller after a night of partial sleep restriction (-36%, p<0.05). Likewise, the amplitude of the vertex N2-P2 was significantly reduced (-34%, p<0.01); also attentional modulation of the N2-P2 was reduced. Thus, objective (LEPs) and subjective (pain ratings) parameters of nociceptive processing were differentially modulated by partial sleep restriction. We propose, that sleep reduction leads to an impairment of activation in the ascending pathway (leading to reduced LEPs). In contradistinction, pain perception was boosted, which we attribute to lack of pain control distinct from classical descending inhibition, and thus not affecting the projection pathway. Sleep-restricted subjects exhibit reduced attentional modulation of pain stimuli and may thus have difficulties to readily attend to or disengage from pain.

Taiji practice attenuates psychobiological stress reactivity - A randomized controlled trial in healthy subjects

Background: Stress reducing effects of Taiji, a mindful and gentle form of body movement, have been reported in previous studies, but standardized and controlled experimental studies are scarce. The present study investigates the effect of regular Taiji practice on psychobiological stress response in healthy men and women. Methods: 70 participants were randomly assigned to either Taiji classes or a waiting list. After 3 months, 26 (8 men, 18 women) persons in the Taiji group and 23 (9 men, 14 women) in the waiting control group underwent a standardized psychosocial stress test combining public speaking and mental arithmetic in front of an audience. Salivary cortisol and α-amylase, heart rate, and psychological responses to psychosocial stress were compared between the study groups. (ClinicalTrials.gov number, NCT01122706.) Results: Stress induced characteristic changes in all psychological and physiological measures. Compared to controls, Taiji participants exhibited a significantly lower stress reactivity of cortisol (p = .028) and heart rate (p = .028), as well as lower α-amylase levels (p = .049). They reported a lower increase in perceived stressfulness (p = .006) and maintained a higher level of calmness (p = .019) in response to psychosocial stress. Conclusion: Our results consistently suggest that practicing Taiji attenuates psychobiological stress reactivity in healthy subjects. This may underline the role of Taiji as a useful mind–body practice for stress prevention.

End-tidal CO(2). An important parameter for a correct interpretation in functional brain studies using speech tasks

The aim was to investigate the effect of different speech tasks, i.e. recitation of prose (PR), alliteration (AR) and hexameter (HR) verses and a control task (mental arithmetic (MA) with voicing of the result on end-tidal CO2 (PETCO2), cerebral hemodynamics and oxygenation. CO2 levels in the blood are known to strongly affect cerebral blood flow. Speech changes breathing pattern and may affect CO2 levels. Measurements were performed on 24 healthy adult volunteers during the performance of the 4 tasks. Tissue oxygen saturation (StO2) and absolute concentrations of oxyhemoglobin ([O2Hb]), deoxyhemoglobin ([HHb]) and total hemoglobin ([tHb]) were measured by functional near-infrared spectroscopy (fNIRS) and PETCO2 by a gas analyzer. Statistical analysis was applied to the difference between baseline before the task, 2 recitation and 5 baseline periods after the task. The 2 brain hemispheres and 4 tasks were tested separately. A significant decrease in PETCO2 was found during all 4 tasks with the smallest decrease during the MA task. During the recitation tasks (PR, AR and HR) a statistically significant (p < 0.05) decrease occurred for StO2 during PR and AR in the right prefrontal cortex (PFC) and during AR and HR in the left PFC. [O2Hb] decreased significantly during PR, AR and HR in both hemispheres. [HHb] increased significantly during the AR task in the right PFC. [tHb] decreased significantly during HR in the right PFC and during PR, AR and HR in the left PFC. During the MA task, StO2 increased and [HHb] decreased significantly during the MA task. We conclude that changes in breathing (hyperventilation) during the tasks led to lower CO2 pressure in the blood (hypocapnia), predominantly responsible for the measured changes in cerebral hemodynamics and oxygenation. In conclusion, our findings demonstrate that PETCO2 should be monitored during functional brain studies investigating speech using neuroimaging modalities, such as fNIRS, fMRI to ensure a correct interpretation of changes in hemodynamics and oxygenation.

Anticipatory cognitive stress appraisal and the acute procoagulant stress response in men

OBJECTIVE: Acute mental stress elicits blood hypercoagulability. Following a transactional stress model, we investigated whether individuals who anticipate stress as more threatening, challenging, and as exceeding their coping skills show greater stress reactivity of the coagulation activation marker D-dimer, indicating fibrin generation in plasma. METHODS: Forty-seven men (mean age 44 +/- 14 years; mean blood pressure [MBP] 101 +/- 12 mm Hg; mean body mass index [BMI] 26 +/- 3 kg/m(2)) completed the Primary Appraisal Secondary Appraisal (PASA) scale before undergoing the Trier Social Stress Test (combination of mock job interview and mental arithmetic task). Heart rate, blood pressure, plasma catecholamines, and D-dimer levels were measured before and after stress, and during recovery up to 60 minutes poststress. RESULTS: Hemodynamic measures, catecholamines, and D-dimer changed across all time points (p values <.001). The PASA "Stress Index" (integrated measure of transactional stress perception) correlated with total D-dimer area under the curve (AUC) between rest and 60 minutes poststress (r = 0.30, p = .050) and with D-dimer change from rest to immediately poststress (r = 0.29, p = .046). Primary appraisal (combined "threat" and "challenge") correlated with total D-dimer AUC (r = 0.37, p = .017), D-dimer stress change (r = 0.41, p = .004), and D-dimer recovery (r = 0.32, p = .042). "Challenge" correlated more strongly with D-dimer stress change than "threat" (p = .020). Primary appraisal (DeltaR(2) = 0.098, beta = 0.37, p = .019), and particularly its subscale "challenge" (DeltaR(2) = 0.138, beta = 0.40, p = .005), predicted D-dimer stress change independently of age, BP, BMI, and catecholamine change. CONCLUSIONS: Anticipatory cognitive appraisal determined the extent of coagulation activation to and recovery from stress in men. Particularly individuals who anticipated the stressor as more challenging and also more threatening had a greater fibrin stress response.

Coagulation activity before and after acute psychosocial stress increases with age

OBJECTIVE: To assess whether stress further increases hypercoagulation in older individuals. We investigated whether acute stress-induced changes in coagulation parameters differ with age. It is known that hypercoagulation occurs in response to acute stress and that a shift in hemostasis toward a hypercoagulability state occurs with age. However, it is not yet known whether acute stress further increases hypercoagulation in older individuals, and thus may increase their risk for cardiovascular disease (CVD). METHODS: A total of 63 medication-free nonsmoking men, aged between 20 and 65 years (mean +/- standard error of the mean = 36.7 +/- 1.7 years), underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. We measured plasma clotting factor VII activity (FVII:C), fibrinogen, and D-dimer at rest, immediately, and 20 minutes after stress. RESULTS: Increased age predicted greater increases in fibrinogen (beta = 0.26, p = 0.041; DeltaR(2) = 0.05), FVII:C (beta = 0.40, p = .006; DeltaR(2) = 0.11), and D-dimer (beta = 0.51, p < .001; DeltaR(2) = 0.18) from rest to 20 minutes after stress independent of body mass index and mean arterial blood pressure. General linear models revealed significant effects of age and stress on fibrinogen, FVII:C, and D-dimer (main effects: p < .04), and greater D-dimer stress reactivity with older age (interaction age-by-stress: F(1.5/90.4) = 4.36, p = .024; f = 0.33). CONCLUSIONS: Our results suggest that acute stress might increase vulnerability in the elderly for hypercoagulability and subsequent hemostasis-associated diseases like CVD.

Aspirin, but not propranolol, attenuates the acute stress-induced increase in circulating levels of interleukin-6: a randomized, double-blind, placebo-controlled study

Psychosocial stress might increase the risk of atherothrombotic events by setting off an elevation in circulating levels of the proinflammatory cytokine interleukin (IL)-6. We investigated the effect of aspirin and propranolol on the responsiveness of plasma IL-6 levels to acute psychosocial stress. For 5 days, 64 healthy subjects were randomized, double-blind, to daily oral aspirin 100mg plus long-acting propranolol 80 mg, aspirin 100mg plus placebo, long-acting propranolol 80 mg plus placebo, or placebo plus placebo. Thereafter, all subjects underwent the 13-min Trier Social Stress Test, which combines a preparation phase, a job interview, and a mental arithmetic task. Plasma IL-6 levels were measured in blood samples collected immediately pre- and post-stress, and 45 min and 105 min thereafter. The change in IL-6 from pre-stress to 105 min post-stress differed between subjects with aspirin medication and those without (p =0.033; eta p2=0.059). IL-6 levels increased less from pre-stress to 105 min post-stress (p <0.027) and were lower (p =0.010) at 105 min post-stress in subjects with aspirin than in subjects without aspirin. The significance of these results was maintained when controlling for gender, age, waist-to-hip ratio, mean arterial blood pressure, and smoking status. Medication with propranolol was not significantly associated with the stress-induced change in IL-6 levels. Also, aspirin and propranolol did not significantly interact in determining the IL-6 stress response. Aspirin but not propranolol attenuated the stress-induced increase in plasma IL-6 levels. This suggests one mechanism by which aspirin treatment might reduce the risk of atherothrombotic events triggered by acute mental stress.

Association of vital exhaustion and depressive symptoms with changes in fibrin D-dimer to acute psychosocial stress

OBJECTIVE: Vital exhaustion and depression are psychosocial risk factors of coronary artery disease. A hypercoagulable state in response to acute psychosocial stress contributes to atherothrombotic events. We aimed to investigate the hypothesis that vital exhaustion and depression correlate with stress-induced changes in the hypercoagulability marker D-dimer. METHODS: Thirty-eight healthy and nonsmoking school teachers (mean age 50+/-8 years, 55% women) completed the nine-item Maastricht Vital Exhaustion Questionnaire and the seven-item depression subscale of the Hospital Anxiety and Depression Scale. Within 1 week, subjects twice underwent the Trier Social Stress Test (i.e., preparation phase, mock job interview, and mental arithmetic that totaled 13 min). Plasma D-dimer levels were determined at five time points during the protocol. RESULTS: Vital exhaustion (P=.022; eta(2)=.080) and depressive symptoms (P=.011; eta(2)=.090) were associated with stress-induced changes in D-dimer levels over time controlling for sex and age. Elevated levels of vital exhaustion (r=-.46, P=.005) and of depression (r=-.51, P=.002) correlated with reduced D-dimer increase from pre-stress to immediately post-stress. Also, elevated vital exhaustion (r=.34, P=.044) and depression (r=.41, P=.013) were associated with increase (i.e., attenuated recovery) of D-dimer levels between 20 and 45 min post-stress. Controlling for stress hormone and blood pressure reactivity did not substantially alter these results. CONCLUSION: The findings suggest an attenuated immediate D-dimer stress response and delayed recovery of D-dimer levels post-stress with elevated vital exhaustion and depressive symptoms. In particular, the prolonged hypercoagulability after stress cessation might contribute to the atherothrombotic risk previously observed with vital exhaustion and depression, even at subclinical levels.

Independent association between lower level of social support and higher coagulation activity before and after acute psychosocial stress

OBJECTIVE: To investigate the relationship between social support and coagulation parameter reactivity to mental stress in men and to determine if norepinephrine is involved. Lower social support is associated with higher basal coagulation activity and greater norepinephrine stress reactivity, which in turn, is linked with hypercoagulability. However, it is not known if low social support interacts with stress to further increase coagulation reactivity or if norepinephrine affects this association. These findings may be important for determining if low social support influences thrombosis and possible acute coronary events in response to acute stress. We investigated the relationship between social support and coagulation parameter reactivity to mental stress in men and determined if norepinephrine is involved. METHODS: We measured perceived social support in 63 medication-free nonsmoking men (age (mean +/- standard error of the mean) = 36.7 +/- 1.7 years) who underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. We measured plasma D-dimer, fibrinogen, clotting Factor VII activity (FVII:C), and plasma norepinephrine at rest as well as immediately after stress and 20 minutes after stress. RESULTS: Independent of body mass index, mean arterial pressure, and age, lower social support was associated with higher D-dimer and fibrinogen levels at baseline (p < .012) and with greater increases in fibrinogen (beta = -0.36, p = .001; DeltaR(2) = .12), and D-dimer (beta = -0.21, p = .017; DeltaR(2) = .04), but not in FVII:C (p = .83) from baseline to 20 minutes after stress. General linear models revealed significant main effects of social support and stress on fibrinogen, D-dimer, and norepinephrine (p < .035). Controlling for norepinephrine did not change the significance of the reported associations between social support and the coagulation measures D-dimer and fibrinogen. CONCLUSIONS: Our results suggest that lower social support is associated with greater coagulation activity before and after acute stress, which was unrelated to norepinephrine reactivity.

Changes in plasma lipids with psychosocial stress are related to hypertension status and the norepinephrine stress response

Hypertension is a known risk factor for cardiovascular disease. Hypertensive individuals show exaggerated norepinephrine (NE) reactivity to stress. Norepinephrine is a known lipolytic factor. It is unclear if, in hypertensive individuals, stress-induced increases in NE are linked with the elevations in stress-induced circulating lipid levels. Such a mechanism could have implications for atherosclerotic plaque formation. In a cross-sectional, quasi-experimentally controlled study, 22 hypertensive and 23 normotensive men (mean +/- SEM, 45 +/- 3 years) underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. We measured plasma NE and the plasma lipid profile (total cholesterol [TC], low-density-lipoprotein cholesterol [LDL-C], high-density-lipoprotein cholesterol, and triglycerides) immediately before and after stress and at 20 and 60 minutes of recovery. All lipid levels were corrected for stress hemoconcentration. Compared with normotensives, hypertensives had greater TC (P = .030) and LDL-C (P = .037) stress responses. Independent of each other, mean arterial pressure (MAP) upon screening and immediate increase in NE predicted immediate stress change in TC (MAP: beta = .41, P = .003; NE: beta = .35, P = .010) and LDL-C (MAP: beta = .32, P = .024; NE: beta = .38, P = .008). Mean arterial pressure alone predicted triglycerides stress change (beta = .32, P = .043) independent of NE stress change, age, and BMI. The MAP-by-NE interaction independently predicted immediate stress change of high-density-lipoprotein cholesterol (beta = -.58, P < .001) and of LDL-C (beta = -.25, P < .08). We conclude that MAP and NE stress reactivity may elicit proatherogenic changes of plasma lipids in response to acute psychosocial stress, providing one mechanism by which stress might increase cardiovascular risk in hypertension.

Prothrombotic changes with acute psychological stress: combined effect of hemoconcentration and genuine coagulation activation

INTRODUCTION: Acute psychosocial stress accelerates blood coagulation and elicits hemoconcentration which mechanisms are implicated in acute coronary thrombotic events. We investigated the extent to which the change in prothrombotic measures with acute stress reflects hemoconcentration and genuine activation of coagulation. MATERIAL AND METHODS: Twenty-one middle-aged healthy men underwent three sessions of a combined speech and mental arithmetic task with one-week intervals. Coagulation and plasma volume were assessed at baseline, immediately post-stress, and 45 min post-stress at sessions one and three. Measures of both visits were aggregated to enhance robustness of individual biological stress responses. Changes in eight coagulation measures with and without adjustment for simultaneous plasma volume shift were compared. RESULTS: From baseline to immediately post-stress, unadjusted levels of fibrinogen (p=0.028), clotting factor VII activity (FVII:C) (p=0.001), FVIII:C (p<0.001), FXII:C (p<0.001), and von Willebrand factor (VWF) (p=0.008) all increased. Taking into account hemoconcentration, fibrinogen (p=0.020) and FVII:C levels (p=0.001) decreased, activated partial prothrombin time (APPT) shortened (p<0.001) and prothrombin time (PT) was prolonged (p<0.001). Between baseline and 45 min post-stress, unadjusted (p=0.050) and adjusted (p=0.001) FVIII:C levels increased, adjusted APTT was prolonged (p=0.017), and adjusted PT was shortened (p=0.033). D-dimer levels did not significantly change over time. CONCLUSIONS: Adjustment for stress-hemoconcentration altered the course of unadjusted levels of several prothrombotic factors. After adjustment for hemoconcentration, APPT was shortened immediately post-stress, whereas 45 min post-stress, FVIII:C was increased and PT was shortened. Procoagulant changes to acute stress may reflect both hemoconcentration and genuine activation of coagulation molecules and pathways.