Low-intensity Stimuli Research Articles

A Novel Botanical Combination Attenuates Light-Induced Retinal Damage through Antioxidant and Prosurvival Mechanisms.

The prevalence of light-induced eye fatigue is increasing globally. Efficient regimen for mitigating light-induced retinal damage is becoming a compelling need for modern society. We investigated the effects of a novel combination of lutein ester, zeaxanthin, chrysanthemum, goji berry, and black currant extracts against retinal damage. In the current work, both in vitro and in vivo light-induced retinal damage models were employed. Animal study showed that under strong light exposure (15000 lx for 2 hours), the a-wave and b-wave from electroretinogram were significantly decreased. Treatment with the combination significantly restored the decrease for b-wave under high- and low-stimulus intensity. Histological analysis reported a substantial decrease in the outer nuclear layer (ONL) thickness in the model group, while the supplementation with the combination significantly improved the ONL thickness. To further explore the underlying mechanism of the protective effects, we utilized ARPE-19 retinal pigment epithelial cell line and found that strong light stimulation (2900 lx for 30 minutes) significantly increased phosphorylation of p38 and JNK and decreased HIF expression. Intriguingly, chrysanthemum, black currant extracts, lutein ester, and zeaxanthin significantly decreased the phosphorylation of p38 and JNK, while chrysanthemum, goji berry, black currant extracts, and lutein ester restored HIF expression. The botanical combination can alleviate light-induced retina damage, potentially through antioxidant and prosurvival mechanisms.

Detection of after-discharges during intraoperative functional brain mapping in awake brain tumor surgery using a novel high-density circular grid

ObjectiveTo evaluate intraoperative use of a novel high-density circular grid in detecting after-discharges (AD) on electrocorticography (ECoG) during functional brain mapping (FBM). MethodsFBM during glioma surgery (10/2016 to 5/2019) recorded ADs using a 22-channel circular grid compared to conventional strip electrodes. ADs were analyzed for detection, duration, amplitude, morphology, histology, direction, and clinical signs. ResultsThirty-two patients (mean age 54.2 years; r = 30–75) with glioma (WHO grade II-IV; 20 grade IV) had surgery. ADs during FBM were more likely in patients with wild-type as opposed to IDH-1 mutants (p < 0.0001) using more contacts compared with linear strip electrodes (p = 0.0001). More sensors tended to be involved in ADs detected by the circular grid vs strips (6.61 vs 3.43; p = 0.16) at lower stimulus intensity (3.14 mA vs 4.13 mA; p = 0.09). No difference in the number of cortical stimulations before resection was present (38.9 mA vs 47.9 mA; p = 0.26). ADs longer than 10 seconds were 32.5 seconds (circular grid) vs 58.4 (strips) (p = 0.12). ConclusionsHigh-density circular grids detect ADs in 360 degrees during FBM for glioma resection. Provocation of ADs was more likely in patients with wild-type than IDH-1 mutation. SignificanceCircular grids offer high-resolution ECoG during intraoperative FBM for detection of ADs.

Effect of intermittent mode of low-intensity vibratory stimuli on bone defect repair

Effect of intermittent mode of low-intensity vibratory stimuli on bone defect repair

Categorical interoception and the role of threat

Interoceptive fears and biased interoception are important characteristics of somatic symptom disorders. Categorization of interoceptive sensations impacts perception of their intensity and unpleasantness. In this study we investigated whether making interoceptive categories threat-relevant further biases interoception of individual sensations compared to safe categories. Either a category containing low- or high-intensity stimuli was made threat-relevant by instructing (and occasionally experiencing) that interoceptive sensations could be followed by an unpredictable electrocutaneous stimulus. We replicated that categorization had a profound impact on perceived interoceptive sensations, with stimuli within categories being perceived as more similar than equidistant stimuli at the category border. We found some evidence for the impact of threat on perceived characteristics of stimuli (with the direction of these effects depending on whether interoceptive stimuli of low or high intensity were threat-relevant), but not for altered categorical choice behaviour. These results imply that the perception of respiratory stimuli is influenced strongly by top-down processes such as categorization, and suggest that interoceptive processing may flexibly adapt to contextual factors such as threat in healthy individuals. However, inflexible responding to repeated and/or severe threat to the internal body may compromise accurate interoception and may result in interoceptive illusions contributing to medically unexplained symptoms and syndromes.

Posteroanterior cervical transcutaneous spinal stimulation targets ventral and dorsal nerve roots

ObjectiveWe aim to non-invasively facilitate activation of spared neural circuits after cervical spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS). We developed and tested a novel configuration for cervical transcutaneous spinal stimulation (cTSS). MethodscTSS was delivered via electrodes placed over the midline at ~T2-T4 levels posteriorly and ~C4-C5 levels anteriorly. Electromyographic responses were measured in arm and hand muscles across a range of stimulus intensities. Double-pulse experiments were performed to assess homosynaptic post-activation depression (PAD). Safety was closely monitored. ResultsMore than 170 cTSS sessions were conducted without major safety or tolerability issues. A cathode-posterior, 2 ms biphasic waveform provided optimal stimulation characteristics. Bilateral upper extremity muscle responses were easily obtained in subjects with SCI and ALS. Resting motor threshold at the abductor pollicis brevis muscle ranged from 5.5 to 51.0 mA. As stimulus intensity increased, response latencies to all muscles decreased. PAD was incomplete at lower stimulus intensities, and decreased at higher stimulus intensities. ConclusionsPosteroanterior cTSS has the capability to target motor neurons both trans-synaptically via large-diameter afferents and non-synaptically via efferent motor axons. SignificancePosteroanterior cTSS is well tolerated and easily activates upper extremity muscles in individuals with SCI and ALS.

Choosing between emotion regulation strategies to appear cool, calm, and collected: Does emotional stimulus intensity matter?

The present study examined the effect of negative emotional stimulus intensity (low versus high) on the choice of emotion regulation (ER) strategy when a person wants to control their emotional expression, and the impact of this choice on how the information accompanying emotional stimuli is remembered. The effects of emotional stimulus intensity on the choice of ER strategy were examined in two studies. In both studies, the participants (unaware of the differences in the intensity of stimuli) were asked to view images inducing negative emotions of high and low intensity and to choose which strategy (cognitive reappraisal or expressive suppression) they would use in order to control their emotional expression. In addition, in Study 2, the authors tested the memory of the verbal content accompanying the emotional stimuli that appeared during the ER period. As expected, the participants chose reappraisal over suppression when confronted with low-intensity stimuli. In contrast, when confronted with high-intensity stimuli, they chose suppression over reappraisal. The results of Study 2 revealed that memory accuracy was higher for those images that the participants chose to use reappraisal rather than suppression.

Peripheral Nerve Ligation Elicits Widespread Alterations in Cortical Sensory Evoked and Spontaneous Activity

Peripheral neuropathies result in adaptation in primary sensory and other regions of cortex, and provide a framework for understanding the localized and widespread adaptations that arise from altered sensation. Mesoscale cortical imaging achieves high temporal resolution of activity using optical sensors of neuronal activity to simultaneously image across a wide expanse of cortex and capture this adaptation using sensory-evoked and spontaneous cortical activity. Saphenous nerve ligation in mouse is an animal model of peripheral neuropathy that produces hyperalgesia circumscribed to the hindlimb. We performed saphenous nerve ligation or sham, followed by mesoscale cortical imaging using voltage sensitive dye (VSD) after ten days. We utilized subcutaneous electrical stimulation at multiple stimulus intensities to characterize sensory responses after ligation or sham, and acquired spontaneous activity to characterize functional connectivity and large scale cortical network reorganization. Relative to sham animals, the primary sensory-evoked response to hindlimb stimulation in ligated animals was unaffected in magnitude at all stimulus intensities. However, we observed a diminished propagating wave of cortical activity at lower stimulus intensities in ligated animals after hindlimb, but not forelimb, sensory stimulation. We simultaneously observed a widespread decrease in cortical functional connectivity, where midline association regions appeared most affected. These results are consistent with localized and broad alterations in intracortical connections in response to a peripheral insult, with implications for novel circuit level understanding and intervention for peripheral neuropathies and other conditions affecting sensation.

Transcranial Magnetic Stimulation-EEG Biomarkers of Poststroke Upper-Limb Motor Function

BackgroundMotor evoked potentials obtained with transcranial magnetic stimulation (TMS) can provide valuable information to inform stroke neurophysiology and recovery but are difficult to obtain in all stroke survivors due to high stimulation thresholds. ObjectiveTo determine whether transcranial magnetic stimulation evoked potentials (TEPs) evoked using a lower stimulus intensity, below that necessary for recording motor evoked potentials, could serve as a marker of poststroke upper-limb motor function and were different compared to healthy adults. MethodsEight chronic stroke survivors (66 ± 21 years) and 15 healthy adults (53 ± 10 years) performed a motor function task using a customized grip-lift manipulandum. TMS was applied to the lesioned motor cortex, with TEPs recorded using simultaneous high-definition electroencephalography (EEG). ResultsStroke participants demonstrated greater hold ratio with the manipulandum. Cluster-based statistics revealed larger P30 amplitude in stroke participants, with significant clusters over frontal (P = .016) and parietal-occipital electrodes (P = .023). There was a negative correlation between the N45 peak amplitude and hold ratio in stroke participants (r = ˗.83, P = .02), but not controls. ConclusionsTEPs can be recorded using lower stimulus intensities in chronic stroke. The global P30 TEP response differed between stroke participants and healthy controls, with results suggesting that the TEP can be used as a biomarker of upper-limb behavior.

Peripheral threat detection in facial expressions by younger and older adults

Everyday threat detection includes recognizing threat cues in facial expressions found in our peripheral visual field. The current study examined age differences in the detection of emotion in low and high intensity angry and fearful facial expressions presented in younger and older adults’ parafoveal (±5°) and peripheral visual field (±10°, ±15°). For both age groups, detection performance was better for higher than for lower intensity stimuli, and detection performance declined with greater peripheral distance. Although younger and older adults displayed a similar pattern of findings for angry facial expressions, younger adults appeared to be more sensitive to lower intensity fearful expressions across all viewing positions. These findings demonstrate that, although threat detection may be partly maintained into older age, neurophysiological changes may accompany aging that selectively reduce older adults’ sensitivity to peripheral facial cues of fear.

The relationship between pain-induced autonomic arousal and perceived duration.

Emotional distortions of the perceived duration of events are often explained in terms of increases and decreases in arousal. While this explanation is theoretically plausible, there is a lack of evidence for a direct relationship between physiological arousal and perceived duration. The aim of the current study was to investigate whether physiological arousal, defined by autonomic nervous system (ANS) activity is directly related to perceived duration. In two experiments we measured skin conductance level (SCL) and high frequency heart rate variability (HF HRV) during verbal estimation tasks. In Experiment 1, participants estimated the duration of electro-cutaneous stimuli previously rated as inducing no pain, low pain and high pain. High intensity stimuli were perceived as lasting for longer than low intensity stimuli, and these changes in duration estimation were associated with changes in ANS activity. In Experiment 2, participants estimated the duration of a neutral visual stimulus while experiencing different intensities of background thermal pain (no pain, low pain, and high pain), to determine whether task-irrelevant arousal also affects time perception. Duration estimations for the neutral stimulus did not increase with pain intensity despite significant increases in SCL. Furthermore, there was no association between ANS activity and time estimation in Experiment 2. These findings suggest that the relationship between physiological arousal and time perception is more complex than previously described. While physiological arousal can influence the perceived duration of events, it appears to have a greater capacity to do so when the to-be-timed stimulus is itself the source of arousal. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

5-Fluorouracil exacerbates cefepime-induced convulsions in pentylenetetrazol-kindled mice

ObjectiveThe antibiotics cefepime and meropenem are recommended for the treatment of neutropenia. However, cefepime has been found to be associated with both peripheral and central adverse events such as renal impairment and seizures, respectively. Previous studies showed that cefepime exacerbated convulsions in corneal kindled mouse models of epilepsy. However, its involvement in chemotherapy-induced side effects is unknown. MethodsIn this study, we examined the convulsive potential of cefepime (500 mg/kg) and meropenem (500 mg/kg) in pentylenetetrazol (PTZ)-kindled mice using an electroconvulsive shock test with low-intensity stimulus currents. Then, the effects of 5-fluorouracil (5-FU, 200 and 400 mg/kg, i.p.) treatment, a model of chemotherapy-induced side effects, were investigated in the PTZ-kindled mouse model. ResultsIn fully PTZ-kindled mice, intravenous administration of cefepime (500 mg/kg) or meropenem (500 mg/kg) did not elicit any convulsions in the electroconvulsive shock test with low-intensity stimulus currents. In the PTZ-kindled mice treated with 5-FU (200 mg/kg), intravenous administration of cefepime (500 mg/kg) exacerbated the convulsions that occurred within 1 min in the electroconvulsive shock test, and the mice subsequently developed convulsive status epilepticus. However, intravenous administration of meropenem (500 mg/kg) did not produce such effects. ConclusionThese findings suggest that the combination of 5-FU and cefepime exacerbates early-onset convulsive seizures and elicits delayed-onset convulsive status epilepticus. Additionally, 5-FU treatment increases the risk of induction of neurotoxic side effects by cefepime.

Factors Associated With Delirium Following Electroconvulsive Therapy: A Systematic Review.

Delirium following electroconvulsive therapy (ECT) has been a clinical challenge, which, however, has not been investigated through a systematic literature review. The objective of this study was to systematically synthesize available evidence regarding factors associated with post-ECT delirium. We conducted a systematic literature search for any type of original investigations that reported risk factors of post-ECT delirium, using PubMed. The literature search identified 43 relevant articles. One study found an association between catatonic feature and increased risk of postictal delirium. Five studies reported that the presence of cerebrovascular disease, Parkinson disease, or dementia was related to higher incidence of post-ECT delirium. Incidence of post-ECT course delirium was increased with bitemporal stimulation (3 studies). One study showed that ultrabrief pulse ECT reduced reorientation time following seizure compared with brief pulse ECT. High stimulus intensity resulted in more prolonged reorientation time after ECT than lower stimulus intensity (2 studies). Longer seizure length was significantly associated with post-ECT delirium in 1 study. Eight studies that examined postictal delirium in association with medications used, including lithium, did not show any consistent finding in their relationships. Four studies showed decreased incidence of postictal delirium in those receiving dexmedetomidine. Limited evidence suggests that catatonic feature, cerebrovascular disease, Parkinson disease, dementia, bitemporal electrode placement, high stimulus intensity, or longer seizure length are associated with an increased risk of post-ECT delirium. Moreover, dexmedetomidine and ultrabrief pulse ECT seem to have preventive effects of post-ECT delirium.

Audiovisual detection at different intensities and delays

In the redundant signals task, two target stimuli are associated with the same response. If both targets are presented together, redundancy gains are observed, as compared with single-target presentation. Different models explain these redundancy gains, including race and coactivation models (e.g., the Wiener diffusion superposition model, Schwarz, 1994, Journal of Mathematical Psychology, and the Ornstein–Uhlenbeck diffusion superposition model, Diederich, 1995, Journal of Mathematical Psychology). In the present study, two monkeys performed a simple detection task with auditory, visual and audiovisual stimuli of different intensities and onset asynchronies. In its basic form, a Wiener diffusion superposition model provided only a poor description of the observed data, especially of the detection rate (i.e., accuracy or hit rate) for low stimulus intensity. We expanded the model in two ways, by (A) adding a temporal deadline, that is, restricting the evidence accumulation process to a stopping time, and (B) adding a second “nogo” barrier representing target absence. We present closed-form solutions for the mean absorption times and absorption probabilities for a Wiener diffusion process with a drift towards a single barrier in the presence of a temporal deadline (A), and numerically improved solutions for the two-barrier model (B). The best description of the data was obtained from the deadline model and substantially outperformed the two-barrier approach.

Classical Conditioning as a Distinct Mechanism of Placebo Effects.

Classical conditioning was suggested as a mechanism of placebo effects in the 1950s. It was then challenged by response expectancy theory, which proposed that classical conditioning is just one of the means by which expectancies are acquired and changed. According to that account, placebo effects induced by classical conditioning are mediated by expectancies. However, in most of the previous studies, either expectancies were not measured or classical conditioning was combined with verbal suggestions. Thus, on the basis of those studies, it is not possible to conclude whether expectancies are involved in placebo effects induced by pure classical conditioning. Two lines of recent studies have challenged the idea that placebo effects induced by classical conditioning are always mediated by expectancies. First, some recent studies have shown that a hidden conditioning procedure elicits both placebo analgesia and nocebo hyperalgesia, neither of which is predicted by expectancy. Second, there are studies showing that visual cues paired with pain stimuli of high or low intensity induce both placebo analgesia and nocebo hyperalgesia when they are presented subliminally without participants’ awareness. The results of both lines of studies suggest that expectancy may not always be involved in placebo effects induced by classical conditioning and that conditioning may be a distinct mechanism of placebo effects. Thus, these results support the idea that placebo effects can be learned by classical conditioning either consciously or unconsciously. However, the existing body of evidence is limited to classically conditioned placebo effects in pain, that is, placebo analgesia and nocebo hyperalgesia.

An eight-week mindfulness-based stress reduction (MBSR) workshop increases regulatory choice flexibility.

Individuals encounter a variety of emotional challenges daily, with optimal emotion modulation requiring adaptive choice among available means of regulation. However, individuals differ in the ability to flexibly and adaptively move between engaging and disengaging emotion regulation (ER) strategies as per contextual demands, referred to as regulatory choice flexibility. Greater regulatory choice flexibility is associated with greater mental health, well-being and resilience, warranting the development of interventions to increase such flexibility. We hypothesized that a mindfulness-based stress reduction (MBSR) program would fulfill this goal. To test our hypothesis, we recruited college students to either participate in an 8-week MBSR workshop or join a waiting list for a later workshop (i.e., control participants). After the workshop's completion, all participants were invited to the laboratory and completed several computerized tasks examining their regulatory choice flexibility when exposed to universally emotion-laden stimuli as well as stimuli specifically related to the students' social and political environment. The regulatory choice patterns of participants who underwent MBSR training were found to be more flexible than those of participants who had not yet completed the workshop, with the former more likely than the latter to favor an engaging ER strategy (i.e., reappraisal) when faced with low-intensity stimuli and a disengaging strategy (i.e., distraction) when faced with high-intensity stimuli. The findings' importance is discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Microstimulation in a spiking neural network model of the midbrain superior colliculus.

The midbrain superior colliculus (SC) generates a rapid saccadic eye movement to a sensory stimulus by recruiting a population of cells in its topographically organized motor map. Supra-threshold electrical microstimulation in the SC reveals that the site of stimulation produces a normometric saccade vector with little effect of the stimulation parameters. Moreover, electrically evoked saccades (E-saccades) have kinematic properties that strongly resemble natural, visual-evoked saccades (V-saccades). These findings support models in which the saccade vector is determined by a center-of-gravity computation of activated neurons, while its trajectory and kinematics arise from downstream feedback circuits in the brainstem. Recent single-unit recordings, however, have indicated that the SC population also specifies instantaneous kinematics. These results support an alternative model, in which the desired saccade trajectory, including its kinematics, follows from instantaneous summation of movement effects of all SC spike trains. But how to reconcile this model with microstimulation results? Although it is thought that microstimulation activates a large population of SC neurons, the mechanism through which it arises is unknown. We developed a spiking neural network model of the SC, in which microstimulation directly activates a relatively small set of neurons around the electrode tip, which subsequently sets up a large population response through lateral synaptic interactions. We show that through this mechanism the population drives an E-saccade with near-normal kinematics that are largely independent of the stimulation parameters. Only at very low stimulus intensities the network recruits a population with low firing rates, resulting in abnormally slow saccades.

Stimulus intensity determined by dose-titration versus age-based methods in electroconvulsive therapy in Thai patients.

ObjectivesThis study aimed to compare the accuracy of the stimulus intensity (SI) calculated by age-based methods with that using the dose-titration method.MethodsThe initial seizure threshold (IST) was determined using a standardized dose titration in hospitalized Thai patients treated with right unilateral (RUL, n=32) and bilateral (BL, n=57) electrode placement. The correlation between the IST and clinical variables was analyzed. The estimated SI based on the patient’s age was compared with the SI determined by dose titration.ResultsAge was highly predictive of the IST for both groups (RUL, P=0.012; BL, P=0.045). Gender (P=0.006) and anticholinergic drug use (P=0.025) predicted the IST for the BL group. For the RUL group, the mean±SD (median) SI estimated using the half-age and age methods was 158±46 (169) mC and 315±92 (338) mC, respectively. The SI determined using the dose-titration method was higher compared with the half-age method and lower compared with the age method. For the RUL group, 31% of subjects using the half-age method and 22% of subjects using the age method would have received an SI within ±20% of that computed using dose titration. Additionally, 19% of subjects using the half-age method and 19% using the age method would have received unacceptably low (<50%) or high (>200%) intensities. For the BL group, 18% of subjects using the half-age method and 32% using the age method would have received an SI within ±20% of that computed using dose titration. Additionally, 39% with the half-age method and 18% with the age method would have received an unacceptably low or high SI, respectively.ConclusionAge strongly predicts the IST, but it does not robustly predict the SI compared with dose titration because the SI calculated using age-based methods results in an unacceptably low or high SI that is associated with a marked risk of adverse effects or inadequate response. We recommend the dose-titration method to determine the SI.

Brain Correlates of Continuous Pain in Rheumatoid Arthritis as Measured by Pulsed Arterial Spin Labeling.

Central nervous system pathways involving pain modulation shape the pain experience in patients with chronic pain. The aims of this study were to understand the mechanisms underlying pain in patients with rheumatoid arthritis (RA) and to identify brain signals that may serve as imaging markers for developing targeted treatments for RA-related pain. Patients with RA and matched control subjects underwent functional magnetic resonance imaging, using pulsed arterial spin labeling. The imaging conditions included 1) resting state, 2) low-intensity stimulus, and 3) high-intensity stimulus. Stimuli consisted of mechanical pressure applied to metacarpophalangeal (MCP) joints with an automated cuff inflator. The low-intensity stimulus was inflation to 30 mm Hg. The high-intensity stimulus was the amount of pressure required to achieve a pain intensity rating of 40 on a 100-point scale for each RA patient, with the same amount of pressure used in the matched control. Among RA patients, regional cerebral blood flow (rCBF) in the medial frontal cortex and dorsolateral prefrontal cortex increased during both low-pressure and high-pressure stimulation. No rCBF changes were observed in pain-free controls. Region-of-interest analyses in RA patients showed that baseline rCBF in the medial frontal cortex was negatively correlated with the pressure required for the high-intensity stimulus and positively correlated with pain induced by the low-intensity stimulus. Baseline rCBF was also marginally correlated with disease activity). Regional CBF during high pain was positively correlated with pain severity and pain interference. In response to clinically relevant joint pain evoked by pressure applied to the MCP joint, neural processing in the medial frontal cortex increases and is directly associated with clinical pain in patients with RA.

Probing short-latency cortical inhibition in the visual cortex with transcranial magnetic stimulation: A reliability study

BackgroundTranscranial magnetic stimulation (TMS) is a non-invasive method to stimulate localized brain regions. Despite widespread use in motor cortex, TMS is seldom performed in sensory areas due to variable, qualitative metrics. ObjectiveAssess the reliability and validity of tracing phosphenes, and to investigate the stimulation parameters necessary to elicit decreased visual cortex excitability with paired-pulse TMS at short inter-stimulus intervals. MethodsAcross two sessions, single and paired-pulse recruitment curves were derived by having participants outline elicited phosphenes and calculating resulting average phosphene sizes. ResultsPhosphene size scaled with stimulus intensity, similar to motor cortex. Paired-pulse recruitment curves demonstrated inhibition at lower conditioning stimulus intensities than observed in motor cortex. Reliability was high across sessions. ConclusionsTMS-induced phosphenes are a valid and reliable tool for measuring cortical excitability and inhibition in early visual areas. Our results also provide appropriate stimulation parameters for measuring short-latency intracortical inhibition in visual cortex.

The Physiopathological Crossroads of Aging

Stress, inflammation and Plasminogen activator inhibitor 1 (PAI-1) are key mechanisms throughout the development of aging, constituting a crossroad in the most frequent pathologies that accompany it. Among metabolic processes, obesity, metabolic syndrome and type 2 diabetes mellitus are included and Alzheimer’s disease among the neurodegenerative processes. Stress is a mechanism of defense of the organism against exogenous and endogenous actions called stressors. In the case of low intensity stimuli, the organism responds with actions aimed at a physiological adaptation (Homeostasis). On the other hand, when a high intensity (experimental level) or chronic stimulus (oxidative stress) is repeated, structural and functional changes are observed in different organs with activation of the hypothalamus-pituitary-adrenal axis, the renin angiotensin system and the sympathetic nervous system, stimulating the production of hormones that release cytokines with proin-flammatory/antiinflammatory properties that play an important role in the previously mentioned pathologies, as well as a marked increase in PAI-1, a gene regulated by stress and by cytokines, with manifest action at the origin of thromboembolic disease, so frequent in aging. The objective of this review is to highlight the importance of the binomial stress and PAI-1 in aging and in the pathologies that accompany it. Because PAI-1 is part of the pathology and complications in aging, some authors suggest the study of PAI-1 inhibitors to achieve its physiological levels, as part of the treatment of these diseases.