PHYSIOLOGY & INFORMATION CONTENT OF FMRI SIGNALS

Key Concepts: hemodynamic response; information content of multivoxel activity patterns, spatiotemporal dynamics of hemodynamic signals

Seminal work on the neural determinants of the fMRI signals both related synaptic and spiking activity to changes in fMRI signals (Logothetis 2002). Upon increased levels of neural activity, multiple signaling pathways induces blood vessels dilation, triggering a localized vascular response involving increased blood flow and volume in the piece of brain involved, that in order to meet the increased metabolic demands. In the paradigmatic case of shifting from a resting (no stimulation) to a high (active) level of neural activity, the increase in blood supply greatly exceeds the increase in oxygen supply. The consequent increase in oxygenation level changes the magnetic properties of the tissue and give rise to the most commonly used fMRI signal, the blood-oxygenation-level-dependent (BOLD) signal.

Temporally, the slow nature of the BOLD response owes to its vascular origin – the vascular response is delayed and sluggish relative to triggering neural. There is however animal (Uhlirova, Kilic et al. 2016) and human (Farivar, Thompson et al. 2011) evidences that the shape of the response, the hemodynamic response function, might not be completely explained by vascular dynamics. Both optogenetic stimulation of specific sub-population of neurons (Uhlirova, Kilic et al. 2016) and modulating the excitation/inhibition ratio of a neural response with targeted visual stimuli (Farivar, Thompson et al. 2011) affected the shape of the hemodynamic response. A main interest in our lab is to establish methodologies for using these differences in temporal shape in order to move from measures of the global level of neural activity within a voxel (from the amplitude of the response) to measures of the qualitative nature of a neural activation like its excitation/inhibition balance (from the shape of the response).

Spatially, patterns of BOLD activation, even at very high resolution, do not perfectly overlap with the pattern of neural activity, being heavily biased toward nearby penetrating and pial veins. That is not to say that spatial patterns of BOLD do not carry information about the underlying spatial pattern of neural activity, which itself can carry important information on neural information processing, the real interesting thing we want to learn about. A privileged approach in our lab to circumvent this issue is to move away from the precise millimeter-range localization of neural processes and rather focus on spatial patterns of BOLD relevant to information processing. This is the decoding approach to fMRI, where the capacity of the multi-voxel pattern of BOLD signal within a brain region to predict features of a visual stimuli is taken as evidence for the processing of that feature in that brain area.

The spatial and temporal characteristics of a BOLD response are intrinsically interrelated through the complex dynamics of adaptive blood flow in the vascular network. A series of experiments in our lab has shown spatiotemporal properties of BOLD signal quite difficult to study with standard approaches. A cardinal findings in our lab is that as the BOLD response unfold through time and space in the visual cortex, the neurally-relevant component (capacity to predict stimulus feature from the spatial pattern) of the response is delayed by an extra 1-2 seconds relative to the largely non-specific (to stimulus feature) BOLD response.

References:

Farivar, R., et al. (2011). "Interocular suppression in strabismic amblyopia results in an attenuated and delayed hemodynamic response function in early visual cortex." Journal of Vision 11(14).

Logothetis, N. K. (2002). "The neural basis of the blood-oxygen-level-dependent functional magnetic resonance imaging signal." Philosophical Transactions of the Royal Society of London Series B-Biological Sciences 357(1424): 1003-1037.

Uhlirova, H., et al. (2016). "Cell type specificity of neurovascular coupling in cerebral cortex." Elife 5.