Brain metabolic fluctuations in absence of stimuli

Abstract

Mapping of brain function with blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) BOLD-MRI relies on the detection of focal changes in cerebral blood flow (CBF) in response to conditioned stimuli. However, in the absence of stimuli, the brain continues to show temporal fluctuations in blood flow as measured with BOLD and perfusion-based MRI (Biswal, NMR. Biomed. 1997). These fluctuations are substantially synchronized across functional regions that have an apparent functional relationship, and therefore might allow mapping and classification of the networks that underlie human brain function without the need for carefully conditioned stimuli. Despite their potential functional siginificance, the origin of the blood flow fluctuations has not been established. Potential sources include cognitive processes, fluctuations in vigilance and conscious awareness, and homeostatic (restorative) processes. Alternatively, the fluctuations might be caused by purely vascular events (e.g. vasomotor effect), without a substantial metabolic or neuronal component. In this study we used MRI methods to establish whether blood flow fluctuations in absence of stimuli subserve a metabolic process. For this purpose, we performed simultaneous BOLD and perfusion MRI at 3.0 T on 7 normal volunteers during a visual task (5 min checkerboard-grey paradigm) and an extended (25 min) rest period. The ratio between BOLD and perfusion changes was used as an indicator of metabolism (Hoge, Proc. Nat. Acad. Sci. 1999). As reference, a 10-minute breath-holding paradigm was inserted between the two conditions. The paradigm consisted of 5 stages of 40 s breath-hold, 80 s normal breathing. Physiologic monitoring included respiratory and cardiac cycles, as well as scalp potentials using a 64-channel EEG system. During rest conditions, we found substantial BOLD and perfusion signal fluctuations in most of neocortex, with strong correlations between functionally related regions. No significant correlations were found with cardiac and respiratory cycles. Frequency analysis of the fluctuations suggested that most energy was concentrated in the 0.01–0.1 Hz band. The strongest fluctuations were observed during early (non-REM) sleep, as identified from EEG. Within visual cortex (VC), the amplitude of the fluctuations reached a level similar to that evoked with the task. BOLD and perfusion signals were highly correlated over most of cortex. The ratio of their fluctuation amplitude in VC averaged 1.66(0.41), 2.82(0.70), and 1.80(0.57) for task, breath holding paradigm, and rest (sleep) respectively. The difference between task and rest was insignificant (p=0.56), while the ratios during task and rest were significantly (p=0.0003/0.017) lower than during the breath-holding paradigm. The lower ratios are indicative of a relatively high oxygen extraction, suggesting involvement of a metabolic process during task and rest, and less so during breathholding. The findings indicate that spatially correlated fluctuations in CBF in absence of stimuli have a metabolic component and continue during early sleep. This has important implication for the design of brain mapping experiments and could shed light on the physiologic processes present during of rest and sleep. Further experiments are planned to investigate a potential role of processes facilitating synaptic plasticity (Huber, Nature 2004).