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- Pavlovian-to-instrumental transfer (1)
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Background
Postoperative delirium is a common disorder in older adults that is associated with higher morbidity and mortality, prolonged cognitive impairment, development of dementia, higher institutionalization rates, and rising healthcare costs. The probability of delirium after surgery increases with patients’ age, with pre-existing cognitive impairment, and with comorbidities, and its diagnosis and treatment is dependent on the knowledge of diagnostic criteria, risk factors, and treatment options of the medical staff. In this study, we will investigate whether a cross-sectoral and multimodal intervention for preventing delirium can reduce the prevalence of delirium and postoperative cognitive decline (POCD) in patients older than 70 years undergoing elective surgery. Additionally, we will analyze whether the intervention is cost-effective.
Methods
The study will be conducted at five medical centers (with two or three surgical departments each) in the southwest of Germany. The study employs a stepped-wedge design with cluster randomization of the medical centers. Measurements are performed at six consecutive points: preadmission, preoperative, and postoperative with daily delirium screening up to day 7 and POCD evaluations at 2, 6, and 12 months after surgery. Recruitment goals are to enroll 1500 patients older than 70 years undergoing elective operative procedures (cardiac, thoracic, vascular, proximal big joints and spine, genitourinary, gastrointestinal, and general elective surgery procedures.
Discussion
Results of the trial should form the basis of future standards for preventing delirium and POCD in surgical wards. Key aims are the improvement of patient safety and quality of life, as well as the reduction of the long-term risk of conversion to dementia. Furthermore, from an economic perspective, we expect benefits and decreased costs for hospitals, patients, and healthcare insurances.
Trial registration
German Clinical Trials Register, DRKS00013311. Registered on 10 November 2017.
In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, p(SVC) = 0.04, x = 26, y = -6, z = -12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (r(s) = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies.
The concurrent performance of cognitive and postural tasks is particularly impaired in old adults and associated with an increased risk of falls. Biological aging of the cognitive and postural control system appears to be responsible for increased cognitive-motor interference effects. We examined neural and behavioral markers of motor-cognitive dual-task performance in young and old adults performing spatial one-back working memory single and dual tasks during semitandem stance. On the neural level, we used EEG to test for age-related modulations in the frequency domain related to cognitive-postural task load. Twenty-eight healthy young and 30 old adults participated in this study. The tasks included a postural single task, a cognitive-postural dual task, and a cognitive-postural triple task (cognitive dual-task with postural demands). Postural sway (i.e., total center of pressure displacements) was recorded in semistance position on an unstable surface that was placed on top of a force plate while performing cognitive tasks. Neural activation was recorded using a 64-channel mobile EEG system. EEG frequencies were attenuated by the baseline postural single-task condition and demarcated in nine Regions-of-Interest (ROIs), i.e., anterior, central, posterior, over the cortical midline, and both hemispheres. Our findings revealed impaired cognitive dual-task performance in old compared to young participants in the form of significantly lower cognitive performance in the triple-task condition. Furthermore, old adults compared with young adults showed significantly larger postural sway, especially in cognitive-postural task conditions. With respect to EEG frequencies, young compared to old participants showed significantly lower alpha-band activity in cognitive-cognitive-postural triple-task conditions compared with cognitive-postural dual tasks. In addition, with increasing task difficulty, we observed synchronized theta and delta frequencies, irrespective of age. Taskdependent alterations of the alpha frequency band were most pronounced over frontal and central ROIs, while alterations of the theta and delta frequency bands were found in frontal, central, and posterior ROIs. Theta and delta synchronization exhibited a decrease from anterior to posterior regions. For old adults, task difficulty was reflected by theta synchronization in the posterior ROI. For young adults, it was reflected by alpha desynchronization in bilateral anterior ROIs. In addition, we could not identify any effects of task difficulty and age on the beta frequency band. Our results shed light on age-related cognitive and postural declines and how they interact. Modulated alpha frequencies during high cognitive-postural task demands in young but not old adults might be reflective of a constrained neural adaptive potential in old adults. Future studies are needed to elucidate associations between the identified age-related performance decrements with task difficulty and changes in brain activity.