Towards an Improved Understanding of BOLD Signal Changes

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DESCRIPTION (provided by applicant): Sharp transients, in electrical recordings, represent a measure of neural activity corresponding to an action potential at a single neuron. Such spike activity reflects the output of a given brain area, yet many regions receive input in the form of excitatory or inhibitory synaptic potentials without generating spikes. This input activity is an important form of computational integration, detected in extracellular recordings as perturbations of the local field potential (LFP). Quantitative analysis of the LFP is performed in the frequency domain, providing a measure of synchronous activity across neurons. Logothetis et al. (2001) showed that BOLD may reflect an area's input in the form of synaptic potentials, rather than its output in the form of spikes. Synaptic inputs can be excitatory or inhibitory, and both forms involve metabolic demands that may alter BOLD and complicate models interpreting BOLD as a proxy for cognitive engagement. The time- courses of oscillations in various frequency bands, and excitatory and inhibitory synaptic potentials, and the relationship between these forms of activity and cognition as reflected by BOLD, is poorly understood. Thus, it is essential to examine the correspondence between certain forms of neural activity, BOLD, and the engagement of cognitive processes. Negative BOLD signals in some cases, for example, demand a nuanced interpretation. The subtractive nature of fMRI initially suggests that negative BOLD simply reflects increased activation during the baseline. However, a number of findings have suggested that negative BOLD represents a distinct phenomenon. This proposal is focused on examining the evidence that negative BOLD reflects decreases in neural activity, associated with cognition. Calibrated MR measures of BOLD and CBF will be performed using tasks previously shown to produce reliable deactivations. These MR measures of flow and oxygenation will be used to determine relative CMRO2 and the oxygen extraction to fully assess the physiologic underpinnings of BOLD. Simultaneous EEC will be recorded and EEC power in multiple frequency bands compared with the MR measures. Much work has been performed characterizing EEC changes in the tasks to be used, but little work has attempted to relate EEC to MR signals. This work will provide insight into the relationship between MR signal changes in cognitive tasks, and EEC changes as measured with surface, and in a limited number of patients, subdural electrodes.