Please cite this article in press as: C. Lucchetti, et al., Neuronal activity reflecting progression of trials in the pre-supplementary motor area of macaque monkey: An expression of neuronal flexibility, Neurosci. Lett. (2011), doi:10.1016/j.neulet.2011.10.043 ARTICLE IN PRESS G Model NSL-28421; No. of Pages 6 Neuroscience Letters xxx (2011) xxx–xxx Contents lists available at SciVerse ScienceDirect Neuroscience Letters jou rn al h om epage: www.elsevier.com/locate/neulet Neuronal activity reflecting progression of trials in the pre-supplementary motor area of macaque monkey: An expression of neuronal flexibility Cristina Lucchetti a,b , Marco Lanzilotto a,b,1 , Vincenzo Perciavalle c , Leopoldo Bon a,b, a Department of Biomedical Sciences, Section of Physiology, University of Modena and Reggio Emilia, I-41125 Modena, Italy b Interdepartment Facilities Center, Section of Polyclinic, University of Modena and Reggio Emilia, I-41125 Modena, Italy c Department of Physiological Sciences, University of Catania, I-95100 Catania, Italy a r t i c l e i n f o Article history: Received 11 April 2011 Received in revised form 13 October 2011 Accepted 15 October 2011 Keywords: Monkey Pre-SMA Trials progression Neuronal flexibility Motor instruction a b s t r a c t We studied the activity of single neurons in the pre-supplementary motor area (pre-SMA) of macaque monkeys as they performed two visuomotor tasks, called the visual fixation task and the visual fixation- blink task. Both tasks involved a sequence of three visual stimuli, red followed by yellow and green. The tasks differed in that the latter one had a gap within the period of the red stimulus, called a “blink”. The tasks were performed in two modes, one of which included movements of both the arm and eye and the other of which involved only eye movements. In the arm–eye mode, the monkeys had to press a bar and fixate the red stimulus that appeared after bar press. To receive a reward, both the bar press and visual fixation had to be maintained until the green stimulus triggered bar release. In the eye mode, bar press and bar release were eliminated from the task. Of the 42 neurons active during the visual fixation task, 15 showed task-related activity in both arm–eye and eye modes, and our analysis focused on these cells. We found that the introduction of the blink in visual fixation-blink task abolished the task-related activity of these cells over the course of 2–4 trials. This finding suggests a role for the pre-SMA in reflecting progression of trials as an updating of motor instruction. © 2011 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Both single-unit recording in monkeys and functional neu- roimaging in humans indicate that the pre-supplementary motor area (pre-SMA), a part of the mesial frontal cortex, is involved in high-level visuomotor associations [6,11,16], the learning and execution of sequential movements [5,13,14,18], switching and updating from automatic to controlled action [7,17], observing and recognizing movements [3,4], execution of “internally” driven actions [7], and the perception and discrimination of durations [9,10]. The function of the pre-SMA can be further explored by manipu- lating visual cues in tasks where such cues provide instructions for eye or arm movements. In the dorsal premotor cortex, for example, Lucchetti et al. [10] studied cell activity during a visual fixation task. They found that neuronal properties changed when the duration of a visual instruction cue was varied or the cue was eliminated. This Corresponding author at: Department of Biomedical Sciences, Section of Physi- ology, University of Modena and Reggio Emilia, I-41125 Modena, Italy. Tel.: +39 0592055360; fax: +39 059428236. E-mail address: leopoldo.bon@unimore.it (L. Bon). 1 Present address: Psychology Department, Princeton University, Princeton, NJ 08540, United States. finding demonstrates neuronal plasticity in the temporal domain, among other properties, and a similar approach can be applied to the pre-SMA. Whereas Lucchetti et al. [10] either removed or varied the duration of a visual cue, the present study explores the effects of adding a new visual event to a given sequence of cues. Accordingly, we recorded the activity of single neurons in the pre-SMA of macaque monkeys as they performed two visuomo- tor tasks: the visual fixation task and the visual fixation-blink task. These two tasks differed from one another in that, in visual fixation- blink task, a visual event (a “blink”) was added to the stimuli presented in the visual fixation task. 2. Methods 2.1. Behavioural methods Two macaque monkeys (Macaca fascicularis, 5- and 6-year-old males) were trained to execute two visuomotor tasks: the visual fix- ation task (VFT) and the visual fixation-blink task (VFBT). Both tasks had two different modes, one involving both arm and eye move- ments (arm–eye mode), the other involving only eye movements (eye mode). Each monkey was seated comfortably in a primate chair, which was located inside a Faraday cage. The monkey was initially condi- tioned to perform the first visuomotor task: VFT in arm–eye mode 0304-3940/$ see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2011.10.043