Impact of anxiety on prefrontal cortex encoding of cognitive flexibility

Abstract

Anxiety often is studied as a stand-alone construct in laboratory models. But in the context of coping with real-life anxiety, its negative impacts extend beyond aversive feelings and involve disruptions in ongoing goal-directed behaviors and cognitive functioning. Critical examples of cognitive constructs affected by anxiety are cognitive flexibility and decision making. In particular, anxiety impedes the ability to shift flexibly between strategies in response to changes in task demands, as well as the ability to maintain a strategy in the presence of distractors. The brain region most critically involved in behavioral flexibility is the prefrontal cortex (PFC), but little is known about how anxiety impacts PFC encoding of internal and external events that are critical for flexible behavior. Here we review animal and human neurophysiological and neuroimaging studies implicating PFC neural processing in anxiety-induced deficits in cognitive flexibility. We then suggest experimental and analytical approaches for future studies to gain a better mechanistic understanding of impaired cognitive inflexibility in anxiety and related disorders.

Caloric restriction preserves memory and reduces anxiety of aging mice with early enhancement of neurovascular functions

“…It has been shown that the changes in anxiety- and depressive-like behavior were correlated with increased levels of dopamine and dopamine metabolites in the midbrain [55]. Our study found that CBF was highly correlated (inversely) with anxiety level, which is consistent with previous findings [4–6]. …”

“…Studies have shown that neurovascular risk is highly associated with accelerated decline in language ability, verbal memory, attention and visuospatial abilities [2, 3]. Reduced CBF is linked to anxiety and depression [4–6], and impaired BBB is associated with neuroinflammation and synaptic dysfunction [7]. These neurovascular deficits are exacerbated with age [8] and in a more rapid and profound fashion in neurodegenerative disorders, including Alzheimer's disease (AD) [9–12].…”

Neuroimaging Biomarkers of Caloric Restriction on Brain Metabolic and Vascular Functions

“…The neurovascular risk is highly associated with accelerated decline in executive functions and cognition, including language, verbal memory, attention and visuospatial abilities [2, 3]. Mental health, such as anxiety and depression, is also link to reduced CBF [4–6], similar to our observations in animal models [50]. …”

“…Similarly, studies have shown that neurovascular risk is highly associated with accelerated decline in language ability, verbal memory, attention and visuospatial abilities [2, 3]. Reduced cerebral blood flow (CBF) is linked to anxiety and depression [4–6], and impaired blood-brain barrier is associated with neuroinflammation and synaptic dysfunction [7]. These metabolic and hemodynamic reductions precede brain structural alteration (gray matter and white matter atrophy) and cognitive impairment [8–10].…”

Anxious to see you: Neuroendocrine mechanisms of social vigilance and anxiety during adolescence

“…Infralimbic cortex has strong functional connections with amygdala (Kim, Gee, Loucks, Davis, & Whalen, 2011), and these projections are essential for effective extinction of fear responses (Bloodgood, Sugam, Holmes, & Kash, 2018;Sierra-Mercado, Padilla-Coreano, & Quirk, 2011). Currently, the functional effects of infralimbic projections to BNST have not been examined, so further study of the impact of anxiety or threat on neural activity within the frontal cortex is needed (Park & Moghaddam, 2017). This is especially true for understanding frontal cortex function in humans.…”