Signal fluctuations in functional magnetic resonance imaging (fMRI) can result from a number of sources that may have a neuronal, physiologic, or instrumental origin. To determine the relative contribution of these sources we recorded physiological (respiration and cardiac) signals simultaneously with fMRI in human volunteers at rest with their eyes closed. State-of-the-art technology was used including high magnetic field (7T), a multi-channel detector array, and high resolution (3 mm3) echo-planar imaging (EPI). We investigated the relative contribution of thermal noise and other sources of variance to the observed fMRI signal fluctuations both in the visual cortex and in the whole brain gray matter. The following sources of variance were evaluated separately: low frequency drifts due to scanner instability, effects correlated with respiratory and cardiac cycles, effects due to variability in the respiratory flow rate and cardiac rate, and other sources, tentatively attributed to spontaneous neuronal activity. We found that low-frequency drifts are the most significant source of fMRI signal fluctuations (3.0% signal change in the visual cortex, TE = 32 ms), followed by spontaneous neuronal activity (2.9%), thermal noise (2.1%) and effects due to variability in physiological rates (respiration 0.9%, heartbeat 0.9%) and correlated with physiological cycles (0.6%). We suggest the selection and use of four lagged physiological noise regressors as an effective model to explain the variance related to fluctuations in the rate of respiration volume change and cardiac pulsation. Our results also indicate that, compared to the whole brain gray matter, the visual cortex has higher sensitivity to changes in both the rate of respiration and in the spontaneous resting state activity. Under the conditions of this study, spontaneous neuronal activity is one of the major contributors to the measured fMRI signal fluctuations, increasing almost two-fold relative to earlier experiments under similar conditions at 3T.

The phenomenon of spontaneous fMRI activity is increasingly being exploited to investigate the connectivity of functional networks in human brain with high spatial-resolution. Although mounting evidence points towards a neuronal contribution to this activity, its functional role and dependence on behavioral state remain unclear. In this work, we used BOLD fMRI at 7 T to study the modulation of spontaneous activity in occipital areas by various behavioral conditions, including resting with eyes closed, eyes open with visual fixation, and eyes open with fixation and focal visual stimulation. Spontaneous activity was separated from evoked activity and from signal fluctuations related to cardiac and respiratory cycles. We found that spontaneous activity in visual areas was substantially reduced (amplitude (44%) and coherence (25%)) with the fixation conditions relative to the eyesclosed condition. No significant further modulation was observed when the visual stimulus was added. The observed dependence on behavioral condition suggests that part of spontaneous fMRI signal fluctuations represents neuronal activity. Possible mechanisms for the modulation of spontaneous activity by behavioral state are discussed. The observed linear superposition of spontaneous fMRI activity with focal evoked activity related to visual processing has important implications for fMRI studies, which ideally should take into account the effect of spontaneous activity to properly define brain activations during task conditions.

Brainstem nuclei (Bn) in humans play a crucial role in vital functions, such as arousal, autonomic homeostasis, sensory and motor relay, nociception, sleep, and cranial nerve function, and they have been implicated in a vast array of brain pathologies. However, an in vivo delineation of most human Bn has been elusive because of limited sensitivity and contrast for detecting these small regions using standard neuroimaging methods. To precisely identify several human Bn in vivo, we employed a 7 Tesla scanner equipped with multi-channel receive-coil array, which provided high magnetic resonance imaging sensitivity, and a multi-contrast (diffusion fractional anisotropy and T2-weighted) echo-planar-imaging approach, which provided complementary contrasts for Bn anatomy with matched geometric distortions and resolution. Through a combined examination of 1.3 mm 3 multi-contrast anatomical images acquired in healthy human adults, we semi-automatically generated in vivo probabilistic Bn labels of the ascending arousal (median and dorsal raphe), autonomic (raphe magnus, periaqueductal gray), and motor (inferior olivary nuclei, two subregions of the substantia nigra compatible with pars compacta and pars reticulata, two subregions of the red nucleus, and, in the diencephalon, two subregions of the subthalamic nucleus) systems. These labels constitute a first step toward the development of an in vivo neuroimaging template of Bn in standard space to facilitate future clinical and research investigations of human brainstem function and pathology. Proof-of-concept clinical use of this template is demonstrated in a minimally conscious patient with traumatic brainstem hemorrhages precisely localized to the raphe Bn involved in arousal.