Catie Chang, Pinar Ozbay, Jacco de Zwart, Dante Picchioni, Miranda Chappel-Farley, Hendrik Mandelkow, Jeff Duyn

While pulse oximetry (PO) is often used with fMRI to provide the timing of heart beats, few studies have focused on fluctuations in the amplitude of PO waveform in the context of fMRI signals. Here, we examine correlations between spontaneous fMRI signals and PO amplitude (POA) variations, observing a strong dependence on vigilance state. During alertness, POA-fMRI correlations were weaker but encompassed regions comprising the default-mode network. During drowsiness and NREM sleep, POA co-varied extensively with BOLD signals across the brain. 

Domenic Cerri, Daniel Albaugh , Brittany Katz, SungHo Lee, Weiting Zhang, Lindsay Walton, Martin MacKinnon, Esteban Oyarzabal, Heather Decot, Nathalie Van Den Berge, Chunxiu Yu, Colleen Mills-Finnerty, Warren Grill, Amit Etkin, Guohong Cui, Garret Stuber, Yen-Yu Ian Shih

Optogenetic stimulation of striatal neurons and several afferents evoke robust negative fMRI responses in the striatum, while striatal electrophysiological recordings during the same stimulations show increases in neuronal activity. Pharmacological manipulations during D1MSN-induced negative striatal responses suggest responses are downstream of MSN activity, but not interneurons or local DA release. Fiber-photometry data from D2MSNs shows a similar pattern of neurovascular uncoupling/negative coupling. This negative fMRI response is also apparent in the human brain. Our results indicate that positive BOLD in the striatum is mediated through DA release, and that negative BOLD in the striatum is induced by local neuronal activations.

Alessio Fracasso, Anna Gaglianese, Serge Dumoulin, Nick Ramsey, Natalia Petridou

Neuroimaging techniques provide a unique window on the study of human brain function in healthy as well as pathological conditions. Intra-cranial electrocorticography (ECoG) at high frequency broadband power is associated with positive blood-oxygenation-level-dependent signal, but the electrophysiological correlates of negative BOLD signals are are less well understood. Here we investigate the relationship between negative BOLD and neuronal population activity measured with ECoG, in humans, using a paradigm that excludes blood stealing as a source of negative BOLD signal.

Betina Ip, Uzay Emir, Andrew Parker, Holly Bridge

We used 7 Tesla combined fMRI-MRS to show that simultaneously measured hemodynamic and neurochemical responses in the human visual cortex changed as a function of visual contrast. BOLD change increased linearly to rise in visual contrast, glutamate increased and GABA decreased. Quantification of this change using an excitation:inhibition index demonstrated a switch from inhibitory-dominant to excitatory-dominant neurochemical response. Our results are a step towards disambiguating contributions of cortical excitation and inhibition to stimulus evoked hemodynamic response.

Eulanca Liu, Jia Guo, Aaron Simon, Frank Haist, David Dubowitz, Richard Buxton

We tested noninvasive methods to measure absolute oxygen metabolism (CMRO₂) in both baseline and activation states without the use of special gases: VSEAN to measure baseline O₂ extraction fraction (OEF), and FLAIR-GESSE to measure R₂’ to estimate the scaling parameter M. Primary findings were: M derived from R₂’ had less variation across subjects compared to hypercapnia-derived M; OEF values were in good agreement with previous PET findings; and, variation of baseline CBF/CMRO₂ coupling across subjects does not follow activation coupling, suggesting different mechanisms may be involved. These results support the potential of gas-free methods for quantitative physiological measurements.

Piero Chiacchiaretta, Antonio Ferretti

Simultaneous acquisition of BOLD and CBF data using ASL allows the study of resting-state brain function from a different perspective with respect to functional connectivity. In particular, recent evidence showed that spontaneous BOLD and CBF fluctuations are strongly coupled in the cortex. Here we show that this coupling is markedly reduced in elderlies with normal cognitive scores, with a regional specific effect in the left supramarginal gyrus, an area known to be involved in different memory functions. These findings suggest that the study of dynamic BOLD-CBF coupling can potentially offer early biomarkers of functional changes in the aging brain. 

Yayan Yin, Yaoyu Zhang, Yang Fan, Bing Wu, Jia-Hong Gao

The development of neuroimaging methods to detect functional oxygen extraction fraction (OEF) is crucial for understanding mechanisms of physiologic function and the underlying neuronal activities. However, dynamic measurement of the OEF is currently limited by the long acquisition time. In this study, a novel pulse sequence using a multiple-offset-spin-echo (MOSE) with an echo-planar imaging (EPI) acquisition scheme was developed to improve the temporal resolution of dynamic OEF measurements. A motor task experiment was performed for ten subjects. The OEF activation maps generated through the proposed technique and compared to traditional blood oxygenation level-dependent (BOLD) activation maps.

Jill De Vis, Xirui Hou, Peiying Liu, Zheyu Wang, Siyuan Cheng, Yang Li, Harshan Ravi, Hanzhang Lu

The relationship between end-tidal (Et) CO₂, and the output measure, BOLD signal, is highly non-linear, due to both physiological non-linearity between cerebral blood flow (CBF) and CO₂ as well as biophysical non-linearity between CBF and BOLD. In this study, we found that, across subjects, baseline EtCO₂ and ΔEtCO₂ inversely influenced the measured CVR values. Therefore, these factors should be taken into account when comparing CVR between groups or patients. However, these inter-subject differences appear to have an independent physiological underpinning, as manipulations of these factors within the subject did not seem to have an effect on the measured CVR values.

Nick Todd, Yongzhi Zhang, Margaret Livingstone, Lino Becerra, David Borsook, Nathan McDannold

Focused ultrasound (FUS) disruption of the blood-brain barrier (BBB) is a promising technology for achieving targeted delivery of pharmacological agents into the brain. While the method has been shown to be safe from the standpoint of not damaging tissue cells, it causes other changes to local physiology that are not fully understood. This study aims to characterize the effects on the hemodynamic response that FUS BBB opening causes. We present BOLD fMRI data showing the effect and preliminary ASL measurements of cerebral blood flow designed to better understand the effect.

Ruiliang Bai, Charles Springer, Dietmar Plenz, Peter Basser

Transmembrane water cycling has long been thought an entirely passive, diffusion-dominated process.  Recent studies suggest that an energetically active water cycling (AWC) mechanism, driven by Na⁺-K⁺-ATPase (NKA) pump activity, also occurs in different cell types, including neurons and astrocytes.  Here we hypothesize that monitoring AWC could provide a new, more direct physical indicator of neuronal activity, which involves much ion cycling and enhanced NKA activity.  By investigating neuronal populations in vitro under resting conditions with spontanotanous activity, and perturbed with tetrodotoxin (TTX), we found TTX simultanously reduces neuronal spiking activity and AWC (by >63%)  suggesting AWC directly reflects neuronal activity.