The development of a novel brain state classifier to investigate the importance of baseline cortical state in neurovascular coupling

Alterations in cortical state as shown by electrophysiological recordings of neural activity are thought to be heavily involved in priming for sensory discrimination (Zagha et al., 2013). A corollary of these cognitive benefits is that state changes have also been shown to have critical effects on global cerebral perfusion (Braun et al., 1997). However at a detailed level, little is known about how changes in state may impact the interpretation of commonly used imaging techniques such as Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) which measure a cerebral vascular response, rather than actual changes in neural activity. In this thesis, a novel automatic brain state classifier (ABSC) algorithm was developed in Chapter 3 and then used to investigate potential differences in haemodynamics during distinct cortical states in Chapters 4 and 5. The ABSC identifies differences in cortical brain state from LFP data by comparing windowed spectral frequency information, with state specific ratios of high to low spectral frequencies, drawn from an initialisation dataset. Using urethane anesthetised rodents allowed recordings of neural signals from 16 channel linear electrodes inserted in the whisker somatosensory and motor cortices respectively. Vascular responses were measured simultaneously with neural recordings, using 2D Optical Imaging Spectroscopy to investigate the impact of these cortical state changes on the concurrent haemodynamics. The ABSC identified two brain states with a high level of accuracy (~90%), compared to expert selection. Separation of state suggests regionally specific alterations in neurovascular parameters. Neurovascular coupling was found to be robust in the whisker barrel cortex, despite state specific changes in the baseline and evoked haemodynamics. In the motor cortex however, the same coupling was not observed with an apparent inversion of coupling found in one of the brain states investigated. The use of the ABSC suggests that spontaneous changes in cortical state may influence cerebral haemodynamics and subsequent evoked responses. The data in this thesis strongly suggests the assessment and categorisation of baseline brain state is necessary for the correct interpretation of blood based imaging such as BOLD fMRI, particularly in the analysis of single trial datasets.