Brain Research Bulletin 82 (2010) 39–45 Contents lists available at ScienceDirect Brain Research Bulletin journal homepage: www.elsevier.com/locate/brainresbull Research report Caffeine enhances frontal relative negativity of slow brain potentials in a task-free experimental setup Carolina Murd a,b , Jaan Aru c,d , Mari Hiio e , Iiris Luiga a,b , Talis Bachmann a,b,∗ a Institute of Public Law, University of Tartu, Kaarli puiestee 3, 10119 Tallinn, Estonia b Institute of Psychology, University of Tartu, 78 Tiigi Street, Tartu, Estonia c Max Planck Institute for Brain Research, Deutschordenstraße 46, 60528 Frankfurt am Main, Germany d Frankfurt Institute for Advanced Studies, Ruth-Moufang-Str. 1, 60438 Frankfurt am Main, Germany e Department of Psychology, Humboldt University, Unter den Linden 6, 10099 Berlin, Germany article info Article history: Received 3 September 2009 Received in revised form 24 December 2009 Accepted 22 January 2010 Available online 1 February 2010 Keywords: Transcranial magnetic stimulation Caffeine Brain state Connectivity Evoked potentials EEG negativity abstract State dependent effects on brain processes are difficult to study due to the task-related confounds. Even in simple task environments external stimuli inevitably interact with dynamically changing states of the brain. Psychopharmacological manipulation and transcranial magnetic stimulation can be used indepen- dently of variations in subject’s experimental task and environmental stimulation. Our aim was to show the investigative potential of combining these two methods for studying the effects of the state of the brain on the dynamics of task-free evoked brain activity. Caffeine was used for inducing higher arousal state and transcranial magnetic stimulation was used to evoke widespread bioelectrical responses of the brain. Occipitally delivered magnetic pulses caused increased global negativity of the brain potentials, but no speed-up of brain potentials when caffeine was administered. The relative negativization effect was most clearly expressed in slow potentials and as measured from frontal and parietal electrodes. This study shows how the causal effects of brain states on neural processes can be studied without the confounding influence of experimental task and stimuli. © 2010 Elsevier Inc. All rights reserved. 1. Introduction While most of the work of the recent decades in neuroscience has been concerned with registration and imaging of brain pro- cesses that unfold in response to specific stimuli in the context of certain experimental tasks, the signatures of these neural pro- cesses and behavior depend on the current state of the brain. Recently, researchers have begun to pay more attention to this aspect of neuroscience [22,28,33]. But this is not easy. Strictly brain state dependent effects on neural processes are difficult to study because behavioral tasks seriously confound brain states as the processes unfold. For example, the default-mode network is deactivated in a task- and stimulus-related manner as a rapidly responding and highly reactive system [48]. At the same time, baseline cortical activity as an indication of the actual brain state considerably determines what the effects of the stimuli are. Thus, oscillatory signatures of awareness of the visual stimuli depend on pre-stimulus state of the visual cortex [53]. More specifically, ∗ Corresponding author at: Institute of Public Law, University of Tartu, Kaarli Puiestee 3, 10119 Tallinn, Harjumaa, Estonia. Tel.: +372 6271891; fax: +372 6271889. E-mail address: talis.bachmann@ut.ee (T. Bachmann). it has been recently shown that the phase of the ongoing pre- stimulus alpha oscillations predicts if a stimulus will be consciously perceived or not [6,34]. Many behavioral and electrophysiological post-stimulus effects depend on the pre-stimulus states of the brain including those related to alpha-band power [1,12,20,26,42,43]. Furthermore, any stimulus from task environment is prone to cause complex effects on both the underlying brain processes (e.g., as measured by EEG/ERP, MEG or fMRI) and on the emotional or arousal states of the subject. The problem is, we do not know what is the relative share of the interactive brain processes deter- mined by the baseline resting state of the brain and the task- and environmental stimulus-related state changes. This is an impor- tant issue because the resting state of the brain interacts with the dynamic changes of functional connectivity and neural synchro- nization during sensorimotor and cognitive demands. In order to have a theoretically and methodologically strong position to reveal task- and environmental stimulus dependent state effects on brain processes we should begin with ascertaining what are the state and process interactions in the brain at its resting state and with- out influences from environmental stimuli. Only then the prime research questions of what are the task-related state dependent effects can be more precisely answered. There are some methods that allow to manipulate states of the brain in a more or less straightforward manner so as to avoid 0361-9230/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.brainresbull.2010.01.013