Oei NY, Tollenaar MS, Elzinga BM, Spinhoven P. Propranolol reduces emotional distraction in working memory: a partial mediating role of propranolol-induced cortisol increases? Neurobiol Learn Mem 93: 388-395
Noradrenalin modulates prefrontal function, such as working memory (WM), and is associated with enhanced distractibility, and enhanced memory for emotional events and stimuli. The beta-blocker propranolol has been shown to reduce memory for emotional stimuli. Herein we describe investigations aimed at assessing whether the administration of propranolol would reduce the interference by emotional distractions during WM performance. In a between-subjects design, 48 young, healthy men received 80 mg propranolol (n=25) or placebo (n=23), before performing an "emotional Sternberg task" with neutral and negatively arousing distracters. Compared to placebo, propranolol impaired WM at low load, however, it also reduced the interference by emotional distracters at high load. Furthermore, an explorative moderated-mediation analysis indicated that the observed propranolol effects on emotional distraction were partially mediated by cortisol. In future non-clinical and clinical memory studies using propranolol administration, cortisol elevations should be monitored to further investigate the potential mediating role of cortisol.
"This result suggests a shift from cognitive/integrative processing to emotion/motor-sensory processing secondary to priming in the context of chronic relational stress. Finally, in this study, participants with conversion disorders performed worse than controls on the subset of cognitive tasks that are known to engage the cognitive capacities and functions of the PFC, suggesting that the PFC's resources were either compromised overall via upregulation of the stress system and high levels of stress hormones (Oei et al., 2010) or being preferentially allocated to emotion/motor-sensory processing. The decreased working memory capacity on multiple subtests of the Digit Span Test and the difficulties in remembering the source of the information on the Memory Recall/Verbal List-Learning Test (as evidenced by the inclusion of words from the wrong list) showed a clear deficit in the cognitive component of PFC function. "
[Show abstract][Hide abstract] ABSTRACT: To assess cognitive function in children and adolescents presenting with acute conversion symptoms.
Fifty-seven participants aged 8.5-18 years (41 girls and 16 boys) with conversion symptoms and 57 age- and gender-matched healthy controls completed the IntegNeuro neurocognitive battery, an estimate of intelligence, and self-report measures of subjective emotional distress.
Participants with conversion symptoms showed poorer performance within attention, executive function, and memory domains. Poorer performance was reflected in more errors on specific tests: Switching of Attention (t(79) = 2.17, p = .03); Verbal Interference (t(72) = 2.64, p = .01); Go/No-Go (t(73) = 2.20, p = .03); Memory Recall and Verbal Learning (interference errors for memory recall; t(61) = 3.13, p < .01); and short-delay recall (t(75) = 2.05, p < .01) and long-delay recall (t(62) = 2.24, p = .03). Poorer performance was also reflected in a reduced span of working memory on the Digit Span Test for both forward recall span (t(103) = -3.64, p < .001) and backward recall span (t(100) = -3.22, p < .01). There was no difference between participants and controls on IQ estimate (t(94) = -589, p = .56), and there was no correlation between cognitive function and perceived distress.
Children and adolescents with acute conversion symptoms have a reduced capacity to manipulate and retain information, to block interfering information, and to inhibit responses, all of which are required for effective attention, executive function, and memory.
Journal of Neuropsychology 01/2014; 9(1). DOI:10.1111/jnp.12037 · 2.49 Impact Factor
"Clonidine and propranolol are lipophilic, penetrate the blood brain barrier, and are used to address the paroxysmal agitation associated with TBI [11,12]. Both drugs have variable effects on memory, emotion, and cognition [36-39]; however, these effects are not defined after TBI. Although the above European data have shown stable cerebral perfusion pressure when using these agents, the early empiric use of these anti-hypertensive agents is considered innovative within North American TBI environments, where feasibility and safety are not clear. "
[Show abstract][Hide abstract] ABSTRACT: Background
Severe TBI, defined as a Glasgow Coma Scale ≤ 8, increases intracranial pressure and activates the sympathetic nervous system. Sympathetic hyperactivity after TBI manifests as catecholamine excess, hypertension, abnormal heart rate variability, and agitation, and is associated with poor neuropsychological outcome. Propranolol and clonidine are centrally acting drugs that may decrease sympathetic outflow, brain edema, and agitation. However, there is no prospective randomized evidence available demonstrating the feasibility, outcome benefits, and safety for adrenergic blockade after TBI.
The DASH after TBI study is an actively accruing, single-center, randomized, double-blinded, placebo-controlled, two-arm trial, where one group receives centrally acting sympatholytic drugs, propranolol (1 mg intravenously every 6 h for 7 days) and clonidine (0.1 mg per tube every 12 h for 7 days), and the other group, double placebo, within 48 h of severe TBI. The study uses a weighted adaptive minimization randomization with categories of age and Marshall head CT classification. Feasibility will be assessed by ability to provide a neuroradiology read for randomization, by treatment contamination, and by treatment compliance. The primary endpoint is reduction in plasma norepinephrine level as measured on day 8. Secondary endpoints include comprehensive plasma and urine catecholamine levels, heart rate variability, arrhythmia occurrence, infections, agitation measures using the Richmond Agitation-Sedation Scale and Agitated Behavior scale, medication use (anti-hypertensive, sedative, analgesic, and antipsychotic), coma-free days, ventilator-free days, length of stay, and mortality. Neuropsychological outcomes will be measured at hospital discharge and at 3 and 12 months. The domains tested will include global executive function, memory, processing speed, visual-spatial, and behavior. Other assessments include the Extended Glasgow Outcome Scale and Quality of Life after Brain Injury scale. Safety parameters evaluated will include cardiac complications.
The DASH After TBI Study is the first randomized, double-blinded, placebo-controlled trial powered to determine feasibility and investigate safety and outcomes associated with adrenergic blockade in patients with severe TBI. If the study results in positive trends, this could provide pilot evidence for a larger multicenter randomized clinical trial. If there is no effect of therapy, this trial would still provide a robust prospective description of sympathetic hyperactivity after TBI.
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