Increased task difficulty results in greater impact of noradrenergic modulation of cognitive flexibility

Abstract

Previous research suggests that the noradrenergic system modulates certain types of cognitive flexibility. This study compared various doses of beta-adrenergic antagonists for their effect on cognitive flexibility in problem solving, and how task difficulty interacts with this effect, as well as the effect of beta-adrenergic antagonists on other tasks. Anagram task performance was compared in 72 subjects using a within-subject design for propranolol at 20 mg, 40 mg, 60 mg, and placebo in a double-blinded manner, and the effects of subject ability and task difficulty were examined. We also examined the effect of the 40 mg propranolol dose on a range of other tasks. Overall, more anagram problems were solved while on propranolol 40 mg than on placebo. Subjects least able to solve the problems benefited significantly from 40 mg of propranolol. Also, for all subjects the most difficult problems were solved more quickly with propranolol 40 mg than placebo. Benefits were also seen for word fluency and backward digit span. Therefore, noradrenergic modulation of cognitive flexibility is affected by how much difficulty the subject is encountering when searching for the solution, a pattern consistent with what might be expected in an effect on the search of the semantic and associative network.

The Role of the Noradrenergic System in Autism Spectrum Disorders

“…However, in each of these studies involving anagrams, whereas performance on propranolol was significantly better than on ephedrine or nadolol, it did not significantly differ from placebo (Beversdorf et al, 1999;Beversdorf et al, 2002). Subsequent research demonstrated that propranolol is beneficial for network flexibility in problem solving particularly when the subject is struggling with the problem (Campbell et al, 2008), as would be expected since greater flexibility would be required for such situations where a greater network search is needed, and can actually impair performance when subjects are solving problems with ease (Campbell et al, 2008). However, in patients where noradrenergic activity is upregulated, such as in cocaine withdrawal, propranolol benefits performance on the simplest problems (Kelley et al, 2007).…”

“…Therefore, we examined the effects of pharmacological agents on network flexibility among individuals with ASD. Specifically, we examined the effect of propranolol on network flexibility in high-functioning adults with ASD using simpler verbal problem-solving tasks with which individuals without neurodevelopmental diagnoses would not be expected to benefit (Campbell et al, 2008). Due to their decreased flexibility of access to networks, we expected that individuals with ASD would have a selective performance benefit from propranolol.…”

Neural reserve, neuronal density in the locus ceruleus, and cognitive decline

“…Dysfunction in this system is thought to contribute to cognitive impairment in several neuropsychiatric disorders (e.g., attention-deficit/hyperactivity disorder, depression). Pharmacologic research has shown that cognition can be enhanced in both affected and unaffected persons by a-2-adrenergic agonists (e.g., guanfacine 34 ), b-adrenergic antagonists (e.g., propranolol 35 ), and norepinephrine transport inhibitors (e.g., atomoxetine 36 ). Further research on the role of the locus ceruleus norepinephrine system in cognitive aging is warranted.…”

Brain Illness and Creativity: Mechanisms and Treatment Risks

“…Beta-blockers such as propranolol can help creative performance anxiety, and may have modest creativity benefits after acute administration. 66 Although there are case reports of propranolol causing depression and decreased libido, larger trials show no statistically significant increase in risk. 81 Benzodiazepines.…”