Abstract
Since its early development in the late 40’s
nuclear magnetic resonance (NMR) has be
come a powerful analytical tool for the investigation of the atomic nucleus and its environment, lending itself to applications ranging from chemical analysis or the study of structures in solids to biomedical investigations. In the early 90’s the potentia
l of this technique for functional brain mapping was demonstrated, causing a great
deal of excitement in both basic and clinical neuroscience. It was shown that by using the appropriate pulse sequences the NMR (or simply MR) imaging technique can be actually made sensitive to local magnetic
susceptibility alterations produced by changes in the concentration of deoxyhemoglobin in venous blood vessels. This blood oxygenation level dependent
(BOLD) contrast mechanism was successfully implemented in awake human subjects as well as in small animals such as rats and cats. In the first part of my talk I shall briefly describe some applications of spatially resolved fMRI in monkeys, including imaging with implanted RF coils. Such studies, in which voxels may cont
ain as few as 600 - 800 cortical neurons, can help us understand how neural networks are organized, and how small cell assemblies contribute to the activation patterns revealed in fMRI. In the second part, I’ll described experiments in which we simultaneous ly traced manganese chloride
and wheat-germ-agglutinin conjugated to horseradish peroxidase (WGA - HRP) to evaluate the specificity of the former by tracing the neuronal connections of the basal ganglia of the monkey. By showing the sequential transport of Mn2+ from striatum to pallidum - substantia nigra and then to thalamus, we demonstrated MRI visualization of transport across at least two synapses in the CNS of the primate. In the last part, I shall present the first results on the neural basis of the BOLD signal. We have recorded local field potentials (LFPs) as well as single- and multi-unit activity (SUA, MUA) in the visual cortex of anesthetized monkeys, and simultaneously collected T2*
- weighted images. Our findings showed that visual stimulation causes a significantly stronger increase in the LFPs than in the MUA, and that the linear transform model predicts the measured fMRI responses well, often explaining more than 90% of the variance in the fMRI signal. LFPs were better predictors than MUA. It is well established that LFPs represent slow waveforms, ncluding synaptic potentials, afterpotentials
of somato-dendritic spikes, and voltage-gated membrane oscillations. Such waveforms reflect both the input of a given cortical area and its local intracortical processing, including the activity of excitatory and inhibitory interneurons. For the most part, MUA represents the spiking of neurons, with single-unit recordings mainly
reporting on the activity of the projection neurons that form the exclusive output of a cortical area. Thus, the fMRI signal is better correlated with the incoming input and the local processing in a given area than it is with the spiking activity. This conclusion was supported by the additional observation that response adaptation - which may decouple the activity of projection neurons from that of interneurons - does not alter the BOLD response. Similarly, neurotransmitter injections during combined electrophysiology and fMRI experiments show unaltered BOLD signal with no spiking act ivity. Finally, experiments will be described that address the issue of whether BOLD can provide us with information on reductions in neural activity. Intracortical recordings in areas showing negative BOLD suggest that the latter follows a strong reduction of both spiking and LFP activity. Finally, on
the basis of all recent fMRI and physiology results I will discuss the contribution of integrative approaches in our understanding of neural mass activity.
