Biology subjects

Festa, E. K.

Publications and source records attributed to Festa, E. K..

3 recordsLinked to original sources

bioRxiv2022

Age-related decline in prefrontal glutamate predicts failure to efficiently deploy working memory in the service of learning

The ability to use past experience to effectively guide decision making declines in older adulthood. Such declines have been theorized to emerge from either impairments of striatal reinforcement learning systems (RL) or impairments of recurrent networks in prefrontal and parietal cortex that support working memory (WM). Distinguishing between these hypotheses has been challenging because either RL or WM could be used to facilitate successful decision making in typical laboratory tasks. Here we investigated the neurocomputational correlates of age-related decision making deficits using an RL-WM task to disentangle these mechanisms, a computational model to quantify them, and magnetic resonance spectroscopy to link them to their molecular bases. Our results reveal that task performance is worse in older age, in a manner best explained by working memory deficits, as might be expected if cortical recurrent networks were unable to sustain persistent activity across multiple trials. Consistent with this, we show that older adults had lower levels of prefrontal glutamate, the excitatory neurotransmitter thought to support persistent activity, compared to younger adults. Individuals with the lowest prefrontal glutamate levels displayed the greatest impairments in working memory after controlling for other anatomical and metabolic factors. Together, our results suggest that lower levels of prefrontal glutamate may contribute to failures of working memory systems and impaired decision making in older adulthood.

animal behavior and cognition↗

bioRxiv2022

Functional Redundancy of the Posterior Hippocampi, but not Anterior Hippocampi or Left Frontal Cortex, is Disrupted in Pathological Brain Aging

As prevalence rates of Alzheimers disease (AD), the leading cause of dementia, are projected to more than double by 2050, emphasis has been placed on early intervention strategies that target resilience mechanisms to delay or prevent the onset of clinical symptoms. Several neural mechanisms underlying brain resilience to AD have been proposed, including redundant neural connections between the posterior hippocampi (HC) and all other brain regions, and global functional connectivity of the left frontal cortex (LFC). It remains unknown, however, if regional redundancy of the HC and LFC underscores neural resilience in the presence of AD pathologies. From the ADNI database, 363 cognitively normal older adults (CN) (N = 220; 36% A{beta}+) and patients with Mild Cognitive Impairment (MCI) (N = 143; 51% A{beta}+) were utilized. Regional redundancy was calculated from resting state fMRI data using a graph theoretical approach by summing the direct and indirect paths (path lengths=1-4) between each ROI and its 262 functional connections. The results showed that A{beta}-status significantly disrupted posterior HC, but not anterior HC or LFC, redundancy. A{beta}- groups showed higher redundancy of the bilateral posterior HC than A{beta}+. In regard to redundancy-cognition relationships, higher posterior HC redundancy was related to better episodic memory performance, an effect which was primarily driven by the A{beta}- group. Despite the positive relationship between posterior HC redundancy and cognition, we did not find compelling evidence that redundancy of the posterior HC serves in a resilience manner, as posterior HC redundancy did not moderate the potentially deleterious relationship between A{beta} deposition and cognition. No relationships were found between anterior HC or LFC redundancy and cognitive performance. Together, these findings suggest that redundancy of the LFC does not underpin its role in resilience and that posterior HC redundancy may capture disruptions to network connectivity that occur as a result of A{beta} deposition.

neuroscience↗

bioRxiv2019

Age-Related Changes in the Neural Dynamics of Bottom-Up and Top-Down Processing During Visual Object Recognition: An Electrophysiological Investigation

When recognizing objects in our environments, we rely on both what we see and what we know. While elderly adults have been found to display increased sensitivity to top-down influences of contextual information during object recognition, the locus of this increased sensitivity remains unresolved. To address this issue, we examined the effects of aging on the neural dynamics of bottom-up and top-down visual processing during rapid object recognition. Specific EEG ERP components indexing bottom-up and top-down processes along the visual processing stream were assessed while systematically manipulating the degree of object ambiguity and scene context congruity. An increase in early attentional feedback mechanisms (as indexed by N1) as well as a functional reallocation of executive attentional resources (as indexed by P200) prior to object identification were observed in elderly adults, while post-perceptual semantic integration (as indexed by N400) remained intact. These findings suggest that compromised bottom-up perceptual processing of visual input in healthy aging leads to an increased involvement of top-down processes to resolve greater perceptual ambiguity during object recognition.

neuroscience↗