Symposium: Neurophysiological basis of BOLD signals

Organizer: Ralph Freeman

List of confirmed speakers in alphabetical order:

Ralph Freeman, "Neurometabolic coupling in the cerebral cortex"

In non-invasive imaging such as fMRI, the blood oxygen level dependent (BOLD) signal is used to infer changes in neural activity. To help establish a direct connection between hemodynamic measurements, and neuronal events, we have developed a technique by which we are able to make simultaneous co-localized measurements of tissue oxygenation and single cell neural activity within the visual cortex. Our findings show that increases in neuronal spike rate are accompanied by decreases in tissue oxygen. This decrease may be used to predict fundamental characteristics of visual processing such as orientation selectivity and ocular dominance. Our results indicate a coupling between neural activity and oxidative metabolism and this may be applied to interpretation of data from functional magnetic resonance imaging. In a separate approach, we have interfered with normal neural processing by use of a relatively noninvasive technique, transcranial magnetic stimulation (TMS). We have applied TMS to the visual cortex, while measuring neural and hemodynamic consequences. Short term pulses can create a prolonged suppression of neural activity. With TMS, there is generally a presence or an absence of spontaneous discharge. These response patterns are partly connected to state- dependent effects. Higher pre-TMS, activity is connected with larger post-TMS response. Our results suggest that the relatively long-lasting neural changes initiated by TMS may be monitored by hemodynamic based neuroimaging.
Myles Jones, "Ongoing neural activity and hemodynamics"

BOLD fMRI has revolutionised cognitive neuroscience as it allows the functional architecture of the brain to be mapped as human subjects perform cognitive or perceptual tasks. However, such techniques rely on the changes in cerebral blood flow, volume and oxygenation (collectively referred to as the hemodynamic response) that accompany evoked neural activity. As such data from imaging experiments has been difficult to interpret in terms of underlying brain activity. Fortunately, animal studies using combinations of electrophysiological, optical and MR techniques have begun to understand the quantitative stimulus-evoked neurovascular coupling that underpins fMRI. In addition to task-related signals there are spontaneous low frequency fluctuations in neuroimaging signals that occur in the absence of stimuli. These fluctuations are increasingly used to infer ongoing pre-stimulus activity and brain connectivity. Their relationship (although implicitly assumed) with underlying neural activity has seldom been investigated. To investigate this issue, optical imaging spectroscopy and multi-channel electrophysiology were used to measure ongoing hemodynamics and neural activity in the somatosensory cortex of anaesthetised rodents. We find that selectivity averaging ongoing hemodynamics at time points corresponding to negative deflections in the ongoing LFP trace results in an identical hemodynamic response function to that observed following presentation of sensory stimuli.
Martin Lauritzen, "Pathway-specific variations in neurovascular and neurometabolic coupling in rodent brain"

Brain blood flow and oxygen metabolism are vital for normal function in the mammalian nervous system, and provides the basis for functional neuroimaging. The presentation will focus on recent progress in our understanding of how neuronal signalling, and in turn information processing, impacts vascular regulation and oxygen metabolism in rat and mice primary somatosensory cortex and cerebellum. Evoked activity induces brief and local changes in blood flow and oxygen metabolism which may be controlled by rapid Ca2+ rises in both pre- and postsynaptic cellular elements, and possibly astrocytes. The high level of energy consumption and blood flow in the resting state is incompletely understood, but non-signalling house-keeping activities play a more important role than hitherto believed. Our data suggest that all types of nerve cell activities use energy, and that there is a linear correlation between synaptic activity and oxygen consumption in most networks. In comparison, the relation between synaptic activity and rises in blood flow is most commonly non-linear. Neurovascular and neurometabolic coupling vary between networks due to activation of different cell types by different synaptic inputs. This is likely to be reflected in the response amplitude and phase of the evoked BOLD signal.
Nikos Logothetis, "Neurovascular Coupling: Insights from Physiology, Neuropharmacology & Electrical Microstimulation"

In my talk I shall describe our current understanding of the neurophysiological and hemodynamic signals, and of the functional neurovascular coupling in the anesthetized and alert behaving monkey. The neurovascular coupling was studied by means of physiological and fMRI experiments, during neuropharmacological blocking of pyramidal cell activity, and with combined electrical microstimulation and fMRI (esfMRI).
Ahalya Viswanathan and Ralph Freeman, "Neurometabolic coupling varies with cortical lamina"

The blood oxygen level-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) is a hemodynamic measurement, which is used to make implications about neural processing. In cerebral cortex, BOLD responses to sensory stimuli are generally averaged across layers. There are clear anatomical and functional differences in laminar cortical organization which imply corresponding variation of BOLD responses. This has been reported in previous visual and somatosensory investigations, but without concurrent measurements of co-localized neural activity. We have modified a multi-channel electrode to provide simultaneous measurements of tissue oxygenation and neural activity in different layers of primary visual cortex. We find laminar differences in tissue oxygen response amplitude. In the middle cortical layers, these differences are independent of local variations in neural activation. Our results suggest that neurometabolic coupling differs across cortical lamina.