Journal of Neuroscience Methods 211 (2012) 40–48 Contents lists available at SciVerse ScienceDirect Journal of Neuroscience Methods journa l h omepa g e: www.elsevier.com/locate/jneumeth Basic Neuroscience Evaluation of brain functional states based on projections of electroencephalographic spectral parameters on 2-dimensional canonical space Seung-Hee Won a,1 , Hwan-Soo Jang a,b , Ho-Won Lee b,c , Il-Sung Jang b,d , Maan-Gee Lee a,b,∗ a Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea b Brain Science and Engineering Institute, Kyungpook National University, Daegu, Republic of Korea c Department of Neurology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea d Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea h i g h l i g h t s ◮ Canonical reference spaces are constructed from EEG parameters by factor analysis. ◮ Two statistical measures, Mahalanobis distance and Hellinger distance, are derived. ◮ The measures evaluate state-discriminating ability of the reference space. ◮ The measures are well correlated with sleep–wake durations after caffeine. ◮ Two statistical measures can describe vigilance and drug-induced states. a r t i c l e i n f o Article history: Received 18 May 2012 Received in revised form 31 July 2012 Accepted 1 August 2012 Keywords: EEG spectral analysis Factor analysis Canonical correlation analysis Mahalanobis distance Hellinger distance a b s t r a c t Electroencephalographic (EEG) activities reflect the functional state of the brain, but it is difficult to objectively describe functional brain states. Here, we describe two statistical divergence measures, Mahalanobis distance and Hellinger distance of projections to the reference spaces, to evaluate their state-discriminating ability. Last, divergence measures of 30-min segments after caffeine treatment were compared to evaluate the dose- and time-dependent arousal effects of caffeine to the best reference space. EEG was recorded from Sprague-Dawley rats during pre- and post-administration of caffeine. Sev- eral two-dimensional reference spaces were constructed from subsets of the normalized 7 relative band powers pooled from the pre-drug period of all recordings for each cortex: two reference spaces from data sets of the frontal and parietal cortex, and four reference spaces from data sets of active wake, slow-wave sleep, paradoxical sleep state, and all states. Sleep–wake states used as test states were plotted onto the reference spaces, and then, two divergence measures were derived to measure state-discriminating ability of each reference space. First, the reference space of the same cortex as test data was better for dis- criminating test states than another cortical reference space. Second, the one reference space constructed from data of all states was better for discriminating test states than the other reference spaces. Third, divergence measures were well correlated with sleep–wake durations after caffeine administration and showed the temporal trends of caffeine-induced arousal effect. These results suggest that two statistical measures can objectively describe brain functional states and drug-induced states. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Analysis of electroencephalographic (EEG) recordings is required to evaluate drug effects. Brain activities, such as, those ∗ Corresponding author at: Department of Pharmacology, School of Medicine, Brain Science and Engineering Institute, Kyungpook National University, 2-101, Dongin-dong, Jung-gu, Daegu 700-422, Republic of Korea. Tel.: +82 53 420 4832; fax: +82 53 426 4703. E-mail address: mglee@knu.ac.kr (M.-G. Lee). URL: http://psyche.knu.ac.kr (M.-G. Lee). 1 Present address: Department of Psychiatry, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. determined by EEG, continuously change due to the processing of internal and external stimuli. A fundamental concept asserts that there are distinct functional states during which the brain produces specific electrical and behavioral states. Therefore, many researchers have tried to estimate functional brain states by using EEG analysis (Gervasoni et al., 2004; John et al., 1983). Drugs pro- duce specific functional states that interact with vigilance states (Kwon et al., 2006; Lee, 1999). Generally, the actions of drugs have been evaluated in stable segments of arbitrary length (5–60 min), which are chosen empirically by experimenters. However, it is difficult to compare drug effects directly because the drug-induced state cannot be evaluated without considering change of the vigi- lance state. Some researchers have separately compared the drug 0165-0270/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jneumeth.2012.08.001