NEURONAL RESPONSES TO A DELAYED-RESPONSE DELAYED-REWARD GO/NOGO TASK IN THE MONKEY POSTERIOR INSULAR CORTEX T. ASAHI, a,d T. UWANO, b,e S. EIFUKU, b R. TAMURA, b,e S. ENDO, d T. ONO a,e AND H. NISHIJO c,e * a Molecular and Integrative Emotional Neuroscience, Graduate School of Medicine, University of Toyama, Toyama 930-0194, Japan b Integrative Neuroscience, Graduate School of Medicine, University of Toyama, Toyama 930-0194, Japan c System Emotional Science, Graduate School of Medicine, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan d Department of Neurosurgery, Graduate School of Medicine, Univer- sity of Toyama, Toyama 930-0194, Japan e Core Research for Evolutional Science and Technology, Japan Sci- ence and Technology Agency, Saitama 332-0012, Japan Abstract—Anatomical connections of the insular cortex suggest its involvement in cognition, emotion, memory, and behavioral manifestation. However, there have been few neurophysiological studies on the insular cortex in primates, in relation to such higher cognitive functions. In the present study, neural activity was recorded from the monkey insular cortex during performance of a delayed- response delayed-reward go/nogo task. In this task, visual stimuli indicating go or nogo responses associated with reward (reward trials) and with no reward (no-reward trials) were presented after eye fixation. In the reward trials, the monkey was required to release a button during presenta- tion of the 2nd visual stimuli after a delay period (delay 1). Then, a juice reward was delivered after another delay (delay 2). The results indicated that the neurons respond- ing in each epoch of the task were topographically local- ized within the insular cortex, consistent with the previous anatomical studies indicating topographical distributions of afferent inputs from other subcortical and cortical sen- sory areas. Furthermore, some insular neurons 1) nonspe- cifically responded to the visual cues and during fixation; 2) responded to the visual cues predicting reward and during the delay period before reward delivery; 3) re- sponded differentially in go/nogo trials during the delay 2; and 4) responded around button manipulation. The ob- served patterns of insular-neuron responses and the cor- respondence of their topographical localization to those in previous anatomical studies suggest that the insular cor- tex is involved in attention- and reward-related functions and might monitor and integrate activities of other brain regions during cognition and behavioral manifestation. © 2006 IBRO. Published by Elsevier Ltd. All rights reserved. Key words: insular cortex, neural responses, go/nogo, de- layed task, reward, monkey. A previous neuroanatomical study has suggested that the orbital-insular-temporopolar region is an integrated cortical region that is part of a paralimbic circuit (Mesulam and Mufson, 1982). The insular cortex, especially its posterior part, is in a unique position to receive information of all sensory modalities: gustation, olfaction, audition, somes- thesis and vision (Mesulam and Mufson, 1982). The pos- terior insula has intimate connections to somatosensory (Friedman et al., 1986) and auditory association areas (Hurst, 1959). The gustatory (Ogawa, 1994) and olfactory (Pribriam et al., 1950; Augustine, 1985) inputs terminate in the anterior division of the insula. Intra-insular connections occur predominantly from the anterior to the posterior sec- tors. The insular cortex also receives visual inputs from the superior temporal sulcus (Mesulam and Mufson, 1982; Seltzer and Pandya, 1991). Consistent with the above anatomical studies, several neurophysiological studies have reported various sensory and complex responses in the primate insular cortex in association with gustatory (Yaxley et al., 1990; Ogawa, 1994), somatosensory (Shneider et al., 1993), cardiovas- cular (Zhang et al., 1999), and vestibular (Grusser et al., 1990) functions. Recent noninvasive imaging studies in humans have demonstrated a role of the insular cortex in complex sensory-motor functions; the insular cortex was implicated in visceral sensory (gustatory, esophageal move- ment), somatosensory (tactile, pain), autonomic (vomiting, cardiovascular function), motor association, and vestibular functions (Augustine, 1996). The insular cortex also has intimate anatomical con- nections with the brain regions implicated in higher brain functions (emotion, cognition, memory, attention, etc.), such as the amygdala (Mufson et al., 1981; Amaral and Price, 1984; Friedman et al., 1986), entorhinal cortex (In- sausti et al., 1987), striatum (Chikama et al., 1997), tem- poropolar (Mesulam and Mufson, 1982; Markowitsch et al., 1985), orbitofrontal (Mesulam and Mufson, 1982; More- craft et al., 1992), cingulate (Mesulam and Mufson, 1982), and perirhinal and parahippocampal cortices (Suzuki and Amaral, 1994). In addition, a posterior part of the insular cortex receives afferent inputs from the cortices related to reward expectancy, e.g. the orbitofrontal cortex (Tremblay *Correspondence to: H. Nishijo, System Emotional Science, Graduate School of Medicine, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan. Tel: +81-76-434-7215; fax: +81-76-434-5012. E-mail address: nishijo@med.u-toyama.ac.jp (H. Nishijo). Abbreviations: BP, button press; BR, button release; CCD, charge- coupled device; DR-DRW, delayed-response delayed-reward go/ nogo; D1, first delay; D2, second delay; EMGs, electromyograms; FIX, fixation period; GNG-D, go/nogo differential; Ia, agranular insula; Id, dysgranular insula; Ig, granular insula; ITI, inter-trial interval; N-D, non-differential; RNR-D, reward/no-reward differential; RW, reward period; SB, start beep; S1, first visual stimulation; S2, second visual stimulation; S2E, end of the second visual stimulation. Neuroscience 143 (2006) 627– 639 0306-4522/06$30.00+0.00 © 2006 IBRO. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.neuroscience.2006.08.008 627