Mapping frontal-limbic correlates of orienting to change detection Leanne M. Williams a,b , Kim Felmingham a,b , Andrew H. Kemp a,b , Chris Rennie a,c , Kerri J. Brown a , Richard A. Bryant a,d and Evian Gordon a,e a TheBrainDynamicsCentre,WestmeadMillenniumInstitute&WesternClinicalSchool,UniversityofSydney,WestmeadHospital, b PsychologicalMedicine, Western Clinical School, c Schoolof Physics,Universityof Sydney, d Schoolof Psychology,Universityof New SouthWales and e Brain Resource International Database, Brain Resource Company,Ultimo,New SouthWales, Sydney, Australia Correspondence andrequests for reprints to Professor Leanne M.Williams,The Brain Dynamics Centre, Acacia House,Westmead Millennium Institute & Western Clinical School,Universityof Sydney,Westmead Hospital,New SouthWales 2145, Sydney, Australia Tel: +612 9845 8195; fax: +612 9845 8190; e-mail: lea@psych.usyd.edu.au Sponsorship:Thisprojectwas fundedby Australian Research Council Linkage (LP0212048) and Discovery (DP0452237) grants, and LMW is fundedby a P¢zer senior research fellowship. Received11September2006; accepted18September2006 Orienting responses are elicited by salient stimuli, and may be indexed by skin conductance responses. Concurrent functional magnetic resonance imaging and skin conductance response recording was used to identify neural correlates of orienting to abruptsensorychange(infrequenthighpitchoddball‘target’tones embedded in frequent lower pitch ‘standard’ tones) in 16 healthy participants. ‘With skin conductance response’ responses to targets were distinguished by preferentially greater activity in the amygdala andventralmedialandlateralfrontalcorticalregions.By contrast,‘without skin conductance response’ responses elicited distinctive activity in the dorsal lateral frontal cortex and supra- marginal gyrus. These ¢ndings suggest that orienting to unex- pected sensory change elicits a network for appraising salience and novelty, whereas, in the absence of orienting, a parallel network for sensory and context evaluation is preferentially engaged. NeuroReport 18:197^202  c 2007 Lippincott Williams & Wilkins. Keywords: amygdala, functionalmagneticresonanceimaging, hippocampus, oddball, orienting, prefrontalcortex, skinconductanceresponses Introduction The detection of significant and unexpected changes in the environment is crucial for survival. Orienting responses (ORs) are a fundamental marker of the registration of stimulus significance or novelty, and mobilization of attention and motor responses [1–4]. In our integrative continuum model, orienting behaviors are considered in relation to a spectrum of stimulus significance [5]. At one extreme, signals with innate motivational significance (such as potential threat) will naturally and automatically engage these orienting mechanisms whereas, at the other extreme, voluntary attention is required to determine the context of a signal in relation to stored information. Skin conductance responses (SCRs) are a robust index of the OR [2,6]. Signals of potential threat elicit SCRs associated with early neural activity before stimulus encoding, and engage the amygdala even in the absence of voluntary attention [7–9]. These findings suggest that amygdala activation contributes to an ‘innate-orienting’ response. On the other hand, the hippocampus has been implicated in the generation of ORs which may rely on more explicit contextual processing and comparison of incoming information to stored regularities [1]. In terms of cortical regions, SCRs have been consistently associated with activation in medial frontal territories (including anterior cingulate). This activation is observed during implicit and explicit stimulus processing, particularly within the ventral portions of these medial frontal areas [9–11]. By contrast, engagement of the lateral prefrontal cortex may, like the hippocampus, rely on more voluntary context processes such as working memory updating [8]. ‘Oddball’ stimuli represent infrequent sensory changes, embedded among frequent standard stimuli, and provide a means to examine the neural correlates of orienting to a fundamental property of threat (abrupt sensory change) in the absence of overt emotional valence [2]. Here, we used concurrent recording of functional magnetic resonance imaging (fMRI) and SCRs during an oddball task to test the hypotheses that (a) a network comprising the amygdala and medial frontal cortical (MFC) areas will be preferentially engaged by SCR orienting to oddball stimuli, reflecting a role in appraising stimulus significance, and (b) a network comprising the hippocampus and lateral frontal cortical (LFC) areas will be preferentially engaged in the absence of SCR orienting, thus reflecting their contribution to contextual processing. Methods Participants Sixteen healthy individuals (eight men, eight women, mean age¼37.8 years, SD¼14.5 years) were recruited for the study in collaboration with the Brain Resource International COGNITIVE NEUROSCIENCE ANDNEUROPSYCHOLOGY NEUROREPORT 0959-4965  c Lippincott Williams & Wilkins Vol 18 No 3 12 February 2007 197 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.