Nikolaidou, S. | Search bioRxiv

bioRxiv2026

Cognitive reserve depends on cortical neurochemistry to predict memory after partner-inflicted brain injury

Memory problems are commonplace following brain injury (BI). However, it remains unclear why some report memory problems while others do not, especially following repeated neurotrauma. Cognitive reserve has been widely hypothesized to account for this variation, but testing this account has yielded inconsistent results and proven difficult, likely as it requires a sample spanning a wide range of BI burden with concurrent neuroimaging and cognitive measurement. Here, we combined a wide range of cognitive assessments with measures of neuronal health using magnetic resonance spectroscopy across three brain regions in 62 women who had experienced physical intimate partner violence. Partner-inflicted BI counts ranged from 0 to 420, yet we found that the number of BIs alone did not explain the variance in memory outcomes. Among a small subset with high BI exposure ([≥]10 BIs; n = 11), BI count explained 5% of the variance in delayed recall, the primary memory outcome, whereas cognitive reserve, inferred from a measure of premorbid functioning, explained almost half (unadjusted in-sample associations). In the full cohort, cognitive reserve predicted memory only among the most heavily injured participants. In a separate model, cognitive reserve predicted memory only when creatine-referenced total N-acetylaspartate, a marker of neuronal health, was lower in the posterior cingulate gyrus and dorsolateral prefrontal cortex. Ultimately, our findings provide behavioral and neurochemical evidence consistent with the cognitive reserve hypothesis and shed new light on why, despite a high burden of neurotrauma, memory may remain resilient.

neuroscience↗

bioRxiv2024

Ketosis Elevates Antioxidants and Enhances Neural Function Through Improved Bioenergetics: A 1H MR Spectroscopy Study

Ketosis is known to alter the balance of neuroactive amino acids and enhance neural function when compared to a glycolytic condition. However, its influence on other metabolites, such as antioxidants and neural energy markers, and the mechanisms by which ketosis improves neural function remain unclear. Here, we measure the neurochemical effects of acute ketosis on the human brain using ultra-high-field 1H MR Spectroscopy (MRS) and investigate the subsequent impact on neural function through resting-state functional magnetic resonance imaging (rsfMRI). In a within-subjects design, N = 63 healthy adults from across the lifespan underwent 1H MRS and rsfMRI scans before and after consuming individually weight-dosed and calorically-matched ketone monoester or glucose drinks. Ketone monoester administration, but not glucose, significantly elevated cerebral antioxidants and energy markers while decreasing GABA, glutamate, and glutamine levels in the posterior cingulate cortex (PCC). Notably, increased bioenergetics, specifically an increase in total creatine, correlated with greater improvements in neural function as measured using rsfMRI. Our results integrate metabolic and functional neuroimaging findings, offering a comprehensive understanding of ketosis-induced changes in brain chemistry and functional network dynamics, yielding valuable insights into potential mechanisms by which ketosis imparts its neural benefits.

neuroscience↗