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Abstract:
Introduction:
Brains are strongly characterized by contextual emergence rather than the much-wished reduction, a fact implying that feature description is necessary but not sufficient condition for comprehending high-level behavior-representations. Contextual conditions of neural networks are a strict requirement for explaining any combination of elementary operations, where rules and dynamical laws can (only) be derived by observing behavior at largely different spatial scales. A multi-scale modeling approach, from single cells to neural mass models is worth attempting, although it still remains one of the central research challenges in computational systems neuroscience.
Here, we combine electrical recordings, stimulation and functional MRI techniques in an attempt to define "states" and potentially their conditional probabilities with respect to well defined internal or external events.
In a companion project we look at Direct Electric Stimulation (DES) of the Locus Coeruleus (LC), the major source of norepinephrine (NE) in the forebrain, which can change spontaneous and task-related neuronal discharge in a large number of LC projection-targets. In fact, the level of NE in the brain modulates a variety of cognitive processes such as attention, perception, learning and memory.
Aims:
1. Characterize electrophysiological and fMRI brain evoked responses to induced stimuli and relate them to the endogenous ongoing activity changes (intensified by the anaesthesia);
2. Discover and quantify the norepinephrine whole brain networks as a response of electrical simulations, LC-DES, or combination of both.
Methods:
We developed a setup for multisite electrophysiological measurement combined with whole-brain imaging and with experimenter induced perturbations, such as sensory, electrical or pharmacological stimulations (Fig,1). Attempting this way to gain deeper insights into the multi-spatiotemporal brain functions.
Results:
Whole brain BOLD maps were obtained for both noxious electrical stimulation and LC-DES. Both produced similar results with an interesting dichotomy, where neocortex and limbic cortex showed mostly negative BOLD responses, while subcortical structures belonging to metencephalon, mesencephalon and diencephalon cortices, presented strong positive BOLD responses. The broadband activity from mPFC recordings show different oscillations regimes. A rapid foot shock (FS) stimulus induces a pronounced transient disruption on the ongoing oscillations during the 'slow oscillation' (SO) synchronized state. A smaller disruption response is observed during 'Active state' (desynchronized) and no disruption under 'Deep SO' (prolonged DOWN state).
Three major cortical states were identified having distinct responses to the same noxious stimulation. The mPFC post-stimulus gamma activity follows a bell-shape curve along the synchronization index (SI), presenting larger responses during the SO state. The analyzed BOLD responses displayed different functional maps according to the cortical SI level. Voxel-wise BOLD maps and fraction of positively (PBR) and negatively (NBR) activated ROIs were computed for the same noxious electrical shock condition and averaged over trials.
Conclusions:
Our results show that it is possible to produce reliable state-dependent whole brain activity maps following electrical stimulation. Measuring fMRI whole brain activity and classifying it according to endogenous cortical electrophysiological states allows us to get a more realistic picture of brain function at multiple spatial and time scales.
