Central feedback of peripheral states of arousal influences motivational behavior and decision making. The sympathetic skin conductance response (SCR) is one index of autonomic arousal. The precise functional neuroanatomy underlying generation and representation of SCR during motivational behavior is undetermined, although it is impaired by discrete brain lesions to ventromedial prefrontal cortex, anterior cingulate, and parietal lobe. We used functional magnetic resonance imaging to study brain activity associated with spontaneous fluctuations in amplitude of SCR, and activity corresponding to generation and afferent representation of discrete SCR events. Regions that covaried with increased SCR included right orbitofrontal cortex, right anterior insula, left lingual gyrus, right fusiform gyrus, and left cerebellum. At a less stringent level of significance, predicted areas in bilateral medial prefrontal cortex and right inferior parietal lobule covaried with SCR. Generation of discrete SCR events was associated with significant activity in left medial prefrontal cortex, bilateral extrastriate visual cortices, and cerebellum. Activity in right medial prefrontal cortex related to afferent representation of SCR events. Activity in bilateral medial prefrontal lobe, right orbitofrontal cortex, and bilateral extrastriate visual cortices was common to both generation and afferent representation of discrete SCR events identified in a conjunction analysis. Our results suggest that areas implicated in emotion and attention are differentially involved in generation and representation of peripheral SCR responses. We propose that this functional arrangement enables integration of adaptive bodily responses with ongoing emotional and attentional states of the organism.

The precise role of orbitofrontal cortex (OFC) in affective processing is still debated. One view suggests OFC represents stimulus reward value and supports learning and relearning of stimulus-reward associations. An alternate view implicates OFC in behavioral control after rewarding or punishing feedback. To discriminate between these possibilities, we used event-related functional magnetic resonance imaging in subjects performing a reversal task in which, on each trial, selection of the correct stimulus led to a 70% probability of receiving a monetary reward and a 30% probability of obtaining a monetary punishment. The incorrect stimulus had the reverse contingency. In one condition (choice), subjects had to choose which stimulus to select and switch their response to the other stimulus once contingencies had changed. In another condition (imperative), subjects had simply to track the currently rewarded stimulus. In some regions of OFC and medial prefrontal cortex, activity was related to valence of outcome, whereas in adjacent areas activity was associated with behavioral choice, signaling maintenance of the current response strategy on a subsequent trial. Caudolateral OFC-anterior insula was activated by punishing feedback preceding a switch in stimulus in both the choice and imperative conditions, indicating a possible role for this region in signaling a change in reward contingencies. These results suggest functional heterogeneity within the OFC, with a role for this region in representing stimulus-reward values, signaling changes in reinforcement contingencies and in behavioral control.

Asperger's syndrome (an autistic disorder) is characterized by stereotyped and obsessional behaviours, and pervasive abnormalities in socio-emotional and communicative behaviour. These symptoms lead to social exclusion and a significant healthcare burden; however, their neurobiological basis is poorly understood. There are few studies on brain anatomy of Asperger's syndrome, and no focal anatomical abnormality has been reliably reported from brain imaging studies of autism, although there is increasing evidence for differences in limbic circuits. These brain regions are important in sensorimotor gating, and impaired 'gating' may partly explain the failure of people with autistic disorders to inhibit repetitive thoughts and actions. Thus, we compared brain anatomy and sensorimotor gating in healthy people with Asperger's syndrome and controls. We included 21 adults with Asperger's syndrome and 24 controls. All had normal IQ and were aged 18-49 years. We studied brain anatomy using quantitative MRI, and sensorimotor gating using prepulse inhibition of startle in a subset of 12 individuals with Asperger's syndrome and 14 controls. We found significant age-related differences in volume of cerebral hemispheres and caudate nuclei (controls, but not people with Asperger's syndrome, had age-related reductions in volume). Also, people with Asperger's syndrome had significantly less grey matter in fronto-striatal and cerebellar regions than controls, and widespread differences in white matter. Moreover, sensorimotor gating was significantly impaired in Asperger's syndrome. People with Asperger's syndrome most likely have generalized alterations in brain development, but this is associated with significant differences from controls in the anatomy and function of specific brain regions implicated in behaviours characterizing the disorder. We hypothesize that Asperger's syndrome is associated with abnormalities in fronto-striatal pathways resulting in defective sensorimotor gating, and consequently characteristic difficulties inhibiting repetitive thoughts, speech and actions.

with ventromedial prefrontal lesions select the high-risk 12 Queen Square strategy (Bechara et al., 1996). In contrast, intact sub-Institute of Neurology jects adopt the more advantageous low-risk strategy University College London with learning (Bechara et al., 1997, 1999). With learn-London WC1N 3BG ing, normal subjects develop anticipatory sympathetic United Kingdom arousal before selecting high-risk options; this anticipa-† Autonomic Unit tory arousal is absent in patients with ventromedial pre-National Hospital for Neurology and Neurosurgery frontal damage, who are indifferent to risk despite nor-London WC1N 3BG mal autonomic responses to such "physical" stimuli as United Kingdom loud noises (Bechara et al., 1996; Tranel, 2000). These ‡ Neurovascular Medicine Unit patients have reduced arousal responses (indexed by St. Mary's Hospital galvanic skin conductance responses [GSR]) to other Imperial College School of Medicine "psychological" stimuli (e.g., affective pictures) (Tranel London W2 1NY and Damasio, 1994; Bechara et al., 1999; Tranel, 2000). United Kingdom The observation of a conjunction between absent anticipatory arousal and maladaptive behavioral strategies has led to a hypothesis that cerebral representation of Summary anticipatory arousal biases behavior and guides strategic decision-making (Damasio et al., 1991; Damasio, We used functional magnetic resonance neuroimag-1994; Bechara et al., 1996). This behavioral bias may be ing to measure brain activity during delay between dissociated from explicit, conscious knowledge about reward-related decisions and their outcomes, and the risk. Healthy subjects show a preference for low-risk modulation of this delay activity by uncertainty and decisions and show increased amplitude of anticipatory arousal. Feedback, indicating financial gain or loss, skin-conductance responses to high-risk options before was given following a fixed delay. Anticipatory arousal developing explicit awareness of the most advantawas indexed by galvanic skin conductance. Delaygeous behavioral strategy (Bechara et al., 1997). Moreperiod activity was associated with bilateral activation over, patients with ventromedial prefrontal cortical lein orbital and medial prefrontal, temporal, and right sions may demonstrate explicit awareness of the risks parietal cortices. During delay, activity in anterior cinassociated with particular decisions but are unable to gulate and orbitofrontal cortices was modulated by modify their behavior accordingly (Saver and Damasio, outcome uncertainty, whereas anterior cingulate, dor-1991; Bechara et al., 1997). Thus, anticipatory arousal is solateral prefrontal, and parietal cortices activity was an index of implicit risk-related learning that may directly modulated by degree of anticipatory arousal. A distinct influence behavior. region of anterior cingulate was commonly activated We used functional magnetic resonance (fMRI) to by both uncertainty and arousal. Our findings highlight measure brain activity in healthy subjects performing a distinct cont...