Red blood cell transfusions are common in patients with sickle cell disease who are at increased risk of stroke. Unfortunately, transfusion thresholds needed to sufficiently dilute sickle red blood cells and adequately restore oxygen delivery to the brain are not well defined. Previous work has shown that transfusion is associated with a reduction in oxygen extraction fraction and cerebral blood flow, both of which are abnormally increased in sickle patients. These reductions are thought to alleviate hemometabolic stress by improving the brain's ability to respond to increased metabolic demand, thereby reducing susceptibility to ischemic injury. Monitoring the cerebral hemometabolic response to transfusion may enable individualized management of transfusion thresholds. Diffuse optical spectroscopies may present a low-cost, non-invasive means to monitor this response. In this study, children with SCD undergoing chronic transfusion therapy were recruited. Diffuse optical spectroscopies (namely, diffuse correlation spectroscopy combined with frequency domain near-infrared spectroscopy) were used to quantify oxygen extraction fraction (OEF), cerebral blood volume (CBV), an index of cerebral blood flow (CBFi), and an index of cerebral oxygen metabolism (CMRO2i) in the frontal cortex immediately before and after transfusion. A subset of patients receiving regular monthly transfusions were measured during a subsequent transfusion. Data was captured from 35 transfusions in 23 patients. Transfusion increased median blood hemoglobin levels (Hb) from 9.1 to 11.7 g/dL (p < 0.001) and decreased median sickle hemoglobin (HbS) from 30.9 to 21.7% (p < 0.001). Transfusion decreased OEF by median 5.9% (p < 0.001), CBFi by median 21.2% (p = 0.020), and CBV by median 18.2% (p < 0.001). CMRO2i did not statistically change from pre-transfusion levels (p > 0.05). Multivariable analysis revealed varying degrees of associations between outcomes (i.e., OEF, CBFi, CBV, and CMRO2i), Hb, and demographics. OEF, CBFi, and CBV were all negatively associated with Hb, while CMRO2i was only associated with age. These results demonstrate that diffuse optical spectroscopies are sensitive to the expected decreases of oxygen extraction, blood flow, and blood volume after transfusion. Diffuse optical spectroscopies may be a promising bedside tool for real-time monitoring and goal-directed therapy to reduce stroke risk for sickle cell disease.

Microvascular cerebral blood flow exhibits pulsatility at the cardiac frequency that carries valuable information about cerebrovascular health. This study used diffuse correlation spectroscopy to quantify normative features of these waveforms in a cohort of thirty healthy adults. We demonstrate they are sensitive to changes in vascular tone, as indicated by pronounced morphological changes with hypercapnia. Further, we observe significant sex-based differences in waveform morphology, with females exhibiting higher flow, greater area-under-the-curve, and lower pulsatility. Finally, we quantify normative values for cerebral critical closing pressure, i.e., the minimum pressure required to maintain flow in a given vascular region.

When we update our episodic memories with new information, mnemonic competition between old and new memories may result because of the presence of shared features. Behavioral studies suggest that this competition can lead to proactive interference, resulting in unsuccessful memory updating, particularly for older adults. It is difficult with behavioral data alone to measure the reactivation of old, overlapping memories during retrieval and its impact on memory for new memories. Here, we applied encoding–retrieval representational similarity (ERS) analysis to EEG data to estimate event-specific encoding-related neural reinstatement of old associations during the retrieval of new ones and its impact on memory for new associations in young and older adults. Our results showed that older adults' new associative memory performance was more negatively impacted by proactive interference from old memories than that of young adults. In both age groups, ERS for old associative memories was greater for trials for which new associative memories were forgotten than remembered. In contrast, ERS for new associative memories was greater when they were remembered than forgotten. In addition, older adults showed relatively attenuated target (i.e., new associates) and lure (i.e., old associates) ERS effects compared to younger adults. Collectively, these results suggest that the neural reinstatement of interfering memories during retrieval contributes to proactive interference across age, whereas overall attenuated ERS effect in older adults might reflect their reduced memory fidelity.

Significance: Cerebrovascular reactivity (CVR), i.e., the ability of cerebral vasculature to dilate or constrict in response to vasoactive stimuli, is a biomarker of vascular health. Exogenous administration of inhaled carbon dioxide, i.e., hypercapnia (HC), remains the "gold-standard" intervention to assess CVR. More tolerable paradigms that enable CVR quantification when HC is difficult/contraindicated have been proposed. However, because these paradigms feature mechanistic differences in action, an assessment of agreement of these more tolerable paradigms to HC is needed.Aim: We aim to determine the agreement of CVR assessed during HC, breath-hold (BH), and resting state (RS) paradigms.Approach: Healthy adults were subject to HC, BH, and RS paradigms. End tidal carbon dioxide (EtCO 2 ) and cerebral blood flow (CBF, assessed with diffuse correlation spectroscopy) were monitored continuously. CVR (%/mmHg) was quantified via linear regression of CBF versus EtCO 2 or via a general linear model (GLM) that was used to minimize the influence of systemic and extracerebral signal contributions.Results: Strong agreement (CCC ≥ 0.69; R ≥ 0.76) among CVR paradigms was demonstrated when utilizing a GLM to regress out systemic/extracerebral signal contributions. Linear regression alone showed poor agreement across paradigms (CCC ≤ 0.35; R ≤ 0.45).Conclusions: More tolerable experimental paradigms coupled with regression of systemic/ extracerebral signal contributions may offer a viable alternative to HC for assessing CVR.