Diffuse correlation spectroscopy (DCS) is a non-invasive optical method for the measurement of blood flow (BF).¹ In DCS, the tissue is illuminated by a long coherence length near-infrared laser, and the speckle pattern formed by moving scatterers, mostly red blood cells, modulates the detected light. The decay of the measured temporal intensity autocorrelation function $[g_2(\tau )]$ originated by the speckle fluctuations provides an index of blood flow (${\mathrm{BF}}_{\mathrm{i}}$),² with units ${\mathrm{cm}}^2/\mathrm{s}$. To maximize the contrast of the measured speckle, single-mode fibers are used, greatly limiting potential photon throughput. Current DCS devices employing single-photon avalanche photodiodes (SPAD) detectors and laser sources at 700 to 850 nm typically operate at a source-detector (SD) separation of 25 mm and an acquisition rate of 1 Hz.³ Larger SD separations are desirable for improving brain sensitivity and reducing scalp signal contamination, especially in the adult population. Faster acquisition rates are needed to detect fast BF dynamics and effectively remove the large pulsatile systemic component from the cerebral signals. Unfortunately, the low signal-to-noise ratio (SNR) of current devices limits the acquisition rates and prevents the use of SD separations $>2.5\mathrm{cm}$.

In premature infants with an extremely low gestational age (ELGA, < 29 weeks GA), dysregulated changes in cerebral blood flow (CBF) are among the major pathogenic factors leading to germinal matrix/intraventricular hemorrhage (GM/IVH). Continuous monitoring of CBF can guide interventions to minimize the risk of brain injury, but there are no clinically standard techniques or tools for its measurement. We report the feasibility of the continuous monitoring of CBF, including measures of autoregulation, via diffuse correlation spectroscopy (DCS) in ELGA infants using CBF variability and correlation with scalp blood flow (SBF, served as a surrogate measure of systemic perturbations). In nineteen ELGA infants (with 9 cases of GM/IVH) monitored for 6–24 h between days 2–5 of life, we found a strong correlation between CBF and SBF in severe IVH (Grade III or IV) and IVH diagnosed within 72 h of life, while CBF variability alone was not associated with IVH. The proposed method is potentially useful at the bedside for the prompt assessment of cerebral autoregulation and early identification of infants vulnerable to GM/IVH.

Objective: This pilot study aims to show the feasibility of noninvasive and real-time cerebral hemodynamic monitoring during carotid endarterectomy (CEA) via diffuse correlation spectroscopy (DCS) and near-infrared spectroscopy (NIRS). Methods: Cerebral blood flow index (CBF_i) was measured unilaterally in seven patients and bilaterally in seventeen patients via DCS. In fourteen patients, hemoglobin oxygenation changes were measured bilaterally and simultaneously via NIRS. Cerebral autoregulation (CAR) and cerebrovascular resistance (CVR) were estimated using CBF_i and arterial blood pressure data. Further, compensatory responses to the ipsilateral hemisphere were investigated at different contralateral stenosis levels. Results: Clamping of carotid arteries caused a sharp increase of CVR (~70%) and a marked decrease of ipsilateral CBF_i (57%). From the initial drop, we observed partial recovery in CBF_i, an increase of blood volume, and a reduction in CVR in the ipsilateral hemisphere. There were no significant changes in compensatory responses between different contralateral stenosis levels as CAR was intact in both hemispheres throughout the CEA phase. A comparison between hemispheric CBF_i showed lower ipsilateral levels during the CEA and post-CEA phases (p < 0.001, 0.03). Conclusion: DCS alone or combined with NIRS is a useful monitoring technique for real-time assessment of cerebral hemodynamic changes and allows individualized strategies to improve cerebral perfusion during CEA by identifying different hemodynamic metrics.

Genetic variants in the oxytocin receptor (OXTR) have been linked to individual differences in social behavior, while aberrant oxytocin regulation is associated with increased susceptibility to neuropsychiatric disorders. Recent magnetic resonance imaging (MRI) studies have demonstrated altered brain morphology and connectivity in response to OXTR single nucleotide polymorphisms (SNP) of GG homozygous compared to targeted allele carriers, such as T or A. However, the sex-specific differences in the structural and connectome-level substrates of OXTR genetic variants and their relationship with endogenous oxytocin remain poorly understood. Therefore, we aimed to decompose structural MRI and functional/structural connectivity to identify sex-specific differences among young adults through OXTR SNPs (rs53576, rs1042778, and rs2254298). High-resolution 3D T1-weighted, resting-state functional, and diffusion tensor images were acquired by sixty-one participants who provided blood samples for quantification of endogenous oxytocin concentrations and use for genotyping, followed by grouping with respect to homozygous and targeted allele carriers. We found that men had greater cortical surface area and sub(cortical) gray matter volume in different homozygous and targeted allele carriers. Resting-state functional and structural connectivity (rsFC and SC, respectively) were allocated differently, primarily in temporal and subcortical brain regions. There were also significant sex-specific differences in mean correlations between endogenous oxytocin and SC, whereas rsFC delineated more significant correlations on the node level. Our results provide valuable insights into sex-specific differences in the structural and connectome-level substrates of OXTR SNPs, contributing to understanding the role of oxytocin in socio-emotional processing and highlighting sex-specific differences in genetic and neural mechanisms underlying social behavior.

Mitochondrial oxidative dysfunction is increasingly implicated in the neuropathophysiology of bipolar disorder (BD), yet in vivo brain assessments of cerebral oxidative metabolism and its relationship with oxygenation have been limited. Here, brain broadband near-infrared spectroscopy (bNIRS) non-invasively measured oxidation of the key enzyme of the mitochondrial electron transport chain, mitochondrial complex IV cytochrome-c-oxidase (oxCCO), alongside oxyhemoglobin (HBO) and deoxyhemoglobin (HBR) measures, in vivo in adults with BD and healthy comparison (HC) during visual stimulation. The relationship between oxCCO and the hemodynamic measures was assessed. During visual stimulation, participants with BD showed significantly higher elevations in oxCCO and significantly lower relative power (concurrence between oxCCO and oxygen use) compared to HC participants, a pattern also observed in euthymic BD participants, suggesting a trait difference in BD. The BD participants also had significantly higher levels of peripheral blood lactate, even when oxCCO levels were high, unlike the association observed for HC participants, which would be expected if oxidative phosphorylation was providing energy to meet neural demands. Together, these findings suggest that to meet neural energy demands, mitochondria in BD exhibit oxygen consumption that is not efficiently coupled to ATP production, and instead shift toward an energetically inefficient process, aerobic glycolysis. By enabling the simultaneous assessment of mitochondrial metabolism and hemodynamics, bNIRS provided a new, scalable, non-invasive tool to uncover mechanisms of neuroenergetic dysfunction in BD. This approach may facilitate the identification of novel mechanistic targets and advance biomarker development for more personalized interventions in mood disorders and potentially other neuropsychiatric disorders.