Showing papers by "Raymond J. Dolan published in 2007"

When Fear Is Near: Threat Imminence Elicits Prefrontal-Periaqueductal Gray Shifts in Humans

Abstract: Humans, like other animals, alter their behavior depending on whether a threat is close or distant. We investigated spatial imminence of threat by developing an active avoidance paradigm in which volunteers were pursued through a maze by a virtual predator endowed with an ability to chase, capture, and inflict pain. Using functional magnetic resonance imaging, we found that as the virtual predator grew closer, brain activity shifted from the ventromedial prefrontal cortex to the periaqueductal gray. This shift showed maximal expression when a high degree of pain was anticipated. Moreover, imminence-driven periaqueductal gray activity correlated with increased subjective degree of dread and decreased confidence of escape. Our findings cast light on the neural dynamics of threat anticipation and have implications for the neurobiology of human anxiety-related disorders.

How the Brain Translates Money into Force: A Neuroimaging Study of Subliminal Motivation

Abstract: Unconscious motivation in humans is often inferred but rarely demonstrated empirically. We imaged motivational processes, implemented in a paradigm that varied the amount and reportability of monetary rewards for which subjects exerted physical effort. We show that, even when subjects cannot report how much money is at stake, they nevertheless deploy more force for higher amounts. Such a motivational effect is underpinned by engagement of a specific basal forebrain region. Our findings thus reveal this region as a key node in brain circuitry that enables expected rewards to energize behavior, without the need for the subjects' awareness.

Reward value coding distinct from risk attitude-related uncertainty coding in human reward systems.

Abstract: When deciding between different options, individuals are guided by the expected (mean) value of the different outcomes and by the associated degrees of uncertainty. We used functional magnetic resonance imaging to identify brain activations coding the key decision parameters of expected value (magnitude and probability) separately from uncertainty (statistical variance) of monetary rewards. Participants discriminated behaviorally between stimuli associated with different expected values and uncertainty. Stimuli associated with higher expected values elicited monotonically increasing activations in distinct regions of the striatum, irrespective of different combinations of magnitude and probability. Stimuli associated with higher uncertainty (variance) elicited increasing activations in the lateral orbitofrontal cortex. Uncertainty-related activations covaried with individual risk aversion in lateral orbitofrontal regions and risk-seeking in more medial areas. Furthermore, activations in expected value-coding regions in prefrontal cortex covaried differentially with uncertainty depending on risk attitudes of individual participants, suggesting that separate prefrontal regions are involved in risk aversion and seeking. These data demonstrate the distinct coding in key reward structures of the two basic and crucial decision parameters, expected value, and uncertainty.

Differential encoding of losses and gains in the human striatum

Abstract: Studies on human monetary prediction and decision making emphasize the role of the striatum in encoding prediction errors for financial reward. However, less is known about how the brain encodes financial loss. Using Pavlovian conditioning of visual cues to outcomes that simultaneously incorporate the chance of financial reward and loss, we show that striatal activation reflects positively signed prediction errors for both. Furthermore, we show functional segregation within the striatum, with more anterior regions showing relative selectivity for rewards and more posterior regions for losses. These findings mirror the anteroposterior valence-specific gradient reported in rodents and endorse the role of the striatum in aversive motivational learning about financial losses, illustrating functional and anatomical consistencies with primary aversive outcomes such as pain.

Threatening a rubber hand that you feel is yours elicits a cortical anxiety response

Abstract: The feeling of body ownership is a fundamental aspect of self-consciousness. The underlying neural mechanisms can be studied by using the illusion where a person is made to feel that a rubber hand is his or her own hand by brushing the person's hidden real hand and synchronously brushing the artificial hand that is in full view. Here we show that threat to the rubber hand can induce a similar level of activity in the brain areas associated with anxiety and interoceptive awareness (insula and anterior cingulate cortex) as when the person's real hand is threatened. We further show that the stronger the feeling of ownership of the artificial hand, the stronger the threat-evoked neuronal responses in the areas reflecting anxiety. Furthermore, across subjects, activity in multisensory areas reflecting ownership predicted the activity in the interoceptive system when the hand was under threat. Finally, we show that there is activity in medial wall motor areas, reflecting an urge to withdraw the artificial hand when it is under threat. These findings suggest that artificial limbs can evoke the same feelings as real limbs and provide objective neurophysiological evidence that the rubber hand is fully incorporated into the body. These findings are of fundamental importance because they suggest that the feeling of body ownership is associated with changes in the interoceptive systems.

The neurobiology of punishment

Abstract: Animals, in particular humans, frequently punish other individuals who behave negatively or uncooperatively towards them. In animals, this usually serves to protect the personal interests of the individual concerned, and its kin. However, humans also punish altruistically, in which the act of punishing is personally costly. The propensity to do so has been proposed to reflect the cultural acquisition of norms of behaviour, which incorporates the desire to uphold equity and fairness, and promotes cooperation. Here, we review the proximate neurobiological basis of punishment, considering the motivational processes that underlie punishing actions.

Separate coding of different gaze directions in the superior temporal sulcus.

Abstract: Summary Electrophysiological recording in the anterior superior temporal sulcus (STS) of monkeys has demonstrated separate cell populations responsive to direct and averted gaze 1, 2. Human functional imaging has demonstrated posterior STS activation in gaze processing, particularly in coding the intentions conveyed by gaze 3, 4, 5, 6, but to date has provided no evidence of dissociable coding of different gaze directions. Because the spatial resolution typical of group-based fMRI studies (∼6–10 mm) exceeds the size of cellular patches sensitive to different facial characteristics (1–4 mm in monkeys), a more sensitive technique may be required. We therefore used fMRI adaptation, which is considered to offer superior resolution [7], to investigate whether the human anterior STS contains representations of different gaze directions, as suggested by non-human primate research. Subjects viewed probe faces gazing left, directly ahead, or right. Adapting to leftward gaze produced a reduction in BOLD response to left relative to right (and direct) gaze probes in the anterior STS and inferior parietal cortex; rightward gaze adaptation produced a corresponding reduction to right gaze probes. Consistent with these findings, averted gaze in the adapted direction was misidentified as direct. Our study provides the first human evidence of dissociable neural systems for left and right gaze.

The human amygdala and orbital prefrontal cortex in behavioural regulation

Abstract: Survival in complex environments depends on an ability to optimize future behaviour based on past experience. Learning from experience enables an organism to generate predictive expectancies regarding probable future states of the world, enabling deployment of flexible behavioural strategies. However, behavioural flexibility cannot rely on predictive expectancies alone and options for action need to be deployed in a manner that is responsive to a changing environment. Important moderators on learning-based predictions include those provided by context and inputs regarding an organism's current state, including its physiological state. In this paper, I consider human experimental approaches using functional magnetic resonance imaging that have addressed the role of the amygdala and prefrontal cortex (PFC), in particular the orbital PFC, in acquiring predictive information regarding the probable value of future events, updating this information, and shaping behaviour and decision processes on the basis of these value representations.

Role of Features and Second-order Spatial Relations in Face Discrimination, Face Recognition, and Individual Face Skills: Behavioral and Functional Magnetic Resonance Imaging Data

Abstract: We compared the contribution of featural information and second-order spatial relations (spacing between features) in face processing. A fully factorial design has the same or different “features” (eyes, mouth, and nose) across two successive displays, whereas, orthogonally, the second-order spatial relations between those features were the same or different. The range of such changes matched the possibilities within the population of natural face images. Behaviorally, we found that judging whether two successive faces depicted the same person was dominated by features, although second-order spatial relations also contributed. This influence of spatial relations correlated, for individual subjects, with their skill at recognition of faces (as famous, or as previously exposed) in separate behavioral tests. Using the same repetition design in functional magnetic resonance imaging, we found feature-dependent effects in the lateral occipital and right fusiform regions. In addition, there were spatial relation effects in the bilateral inferior occipital gyrus and right fusiform that correlated with individual differences in (separately measured) behavioral sensitivity to those changes. The results suggest that featural and second-order spatial relation aspects of faces make distinct contributions to behavioral discrimination and recognition, with features contributing most to face discrimination and second-order spatial relational aspects correlating best with recognition skills. Distinct neural responses to these aspects were found with functional magnetic resonance imaging, particularly when individual skills were taken into account for the impact of second-order spatial relations.

Mechanisms of top-down facilitation in perception of visual objects studied by FMRI.

Abstract: Prior knowledge regarding the possible identity of an object facilitates its recognition from a degraded visual input, though the underlying mechanisms are unclear. Previous work implicated ventral visual cortex but did not disambiguate whether activity-changes in these regions are causal to or merely reflect an effect of facilitated recognition. We used functional magnetic resonance imaging to study top-down influences on processing of gradually revealed objects, by preceding each object with a name that was congruent or incongruent with the object. Congruently primed objects were recognized earlier than incongruently primed, and this was paralleled by shifts in activation profiles for ventral visual, parietal, and prefrontal cortices. Prior to recognition, defined on a trial-by-trial basis, activity in ventral visual cortex rose gradually but equivalently for congruently and incongruently primed objects. In contrast, prerecognition activity was greater with congruent priming in lateral parietal, retrosplenial, and lateral prefrontal cortices, whereas functional coupling between parietal and ventral visual (and also left lateral prefrontal and parietal) cortices was enhanced in the same context. Thus, when controlling for recognition point and stimulus information, activity in ventral visual cortex mirrors recognition success, independent of condition. Facilitation by top-down cues involves lateral parietal cortex interacting with ventral visual areas, potentially explaining why parietal lesions can lead to deficits in recognizing degraded objects even in the context of top-down knowledge.

Distinct and convergent visual processing of high and low spatial frequency information in faces.

Abstract: We tested for differential brain response to distinct spatial frequency (SF) components in faces. During a functional magnetic resonance imaging experiment, participants were presented with "hybrid" faces containing superimposed low and high SF information from different identities. We used a repetition paradigm where faces at either SF range were independently repeated or changed across consecutive trials. In addition, we manipulated which SF band was attended. Our results suggest that repetition and attention affected partly overlapping occipitotemporal regions but did not interact. Changes of high SF faces increased responses of the right inferior occipital gyrus (IOG) and left inferior temporal gyrus (ITG), with the latter response being also modulated additively by attention. In contrast, the bilateral middle occipital gyrus (MOG) responded to repetition and attention manipulations of low SF. A common effect of high and low SF repetition was observed in the right fusiform gyrus (FFG). Follow-up connectivity analyses suggested direct influence of the MOG (low SF), IOG, and ITG (high SF) on the FFG responses. Our results reveal that different regions within occipitotemporal cortex extract distinct visual cues at different SF ranges in faces and that the outputs from these separate processes project forward to the right FFG, where the different visual cues may converge.

Experience-dependent coding of facial expression in superior temporal sulcus.

Abstract: Sensory information from the external world is inherently ambiguous, necessitating prior experience as a constraint on perception. Prolonged experience (adaptation) induces perception of ambiguous morph faces as a category different from the adapted category, suggesting sensitivity in underlying neural codes to differences between input and recent experience. Using magnetoencephalography, we investigated the neural dynamics of such experience-dependent visual coding by focusing on the timing of responses to morphs after facial expression adaptation. We show that evoked fields arising from the superior temporal sulcus (STS) reflect the degree to which a morph and adapted expression deviate. Furthermore, adaptation effects within STS predict the magnitude of behavioral aftereffects. These findings show that the STS codes expressions relative to recent experience rather than absolutely and may bias perception of expressions. One potential neural mechanism for the late timing of both effects appeals to hierarchical models that ascribe a central role to backward connections in mediating predictive codes.

Social Regulation of Affective Experience of Humor

Abstract: The element of surprise, a necessary condition for the experience of humor, often derives from the fact that the alternative interpretation/resolution offered by the punch line of a joke is physically or socially forbidden. Children's humor typifies violation of physical norms, whereas adult humor typically pushes the boundaries of social norms. Excess norm violation, to the point of offending, can attenuate the experience of humor/mirth. To examine the neural basis of regulation of affective experience of humor by social norms, we scanned 16 normal subjects while they viewed a series of cartoons that varied in funniness and social acceptability. Behavioral results indicated two separate groups of subjects, those who found the cartoons less offensive and those who found them more offensive. In the group that found the jokes more offensive, there was a negative correlation between funniness and social inappropriateness. In this group, the corresponding Humor by Social inappropriateness interaction during functional magnetic resonance imaging revealed enhanced activation in the right hippocampus along with relative deactivation in the ventral medial prefrontal cortex (VMPFC). By contrast, the Funniness by Social appropriateness interaction resulted in activation in the VMPFC and relative deactivation in the right hippocampus. These results suggest that the regulation of humor by social norms involves reciprocal response patterns between VMPFC and hippocampus regions implicated in contextual regulation of behavior and memory, respectively.

Decision-Making Dysfunctions in Psychiatry—Altered Homeostatic Processing?

Abstract: affect us—hasrelevancefromthebroadestlevelsof public policy to our most immediate inter-personalinteractions.Thereislittledoubtthatthecombination of Game Theory tasks, with theirformal, detailed mathematical models, and thetechniquesofmodernneuroscienceoffersfruitfulopportunities for the study of social decision-making. This approach can both advance thepredictive accuracy of theoretical models byconstraining them based on behavioral perform-ance and the underlying neurobiology, as well asfurther our knowledge of how people makedecisions in a social context.

Vagus Nerve Stimulation for Treatment-Resistant Depression: Behavioral and Neural Effects on Encoding Negative Material

Abstract: Objectives: Vagus nerve stimulation (VNS) can improve depression. Cognitive models of depression highlight an over-representation of negative thoughts and memories, with depressed individuals showing memory facilitation for negative material. We hypothesized that the antidepressant action of VNS may emerge through corrective influences on ‘negativity bias’ in memory. We therefore examined the impact of VNS on emotional memory and its underlying brain activity. Methods: We tested a single patient undergoing VNS for treatment-resistant depression (TRD). Stimulation was set at a 30/66-second on/off cycle during three encoding blocks when the patient viewed randomly presented positive, negative, and neutral words. Following each block, VNS was switched off and the patient identified previously seen words from distractors in a subsequent recognition memory task. The patient was scanned using functional magnetic resonance imaging (fMRI) during the first encoding block. Results: There was robust recall of negative material viewed during ‘off’ cycles of VNS but subsequent memory of negative words was attenuated during active VNS (‘on’ cycles). VNS did not influence memory for neutral and positive words. With neuroimaging, direct modulatory effects of VNS were observed in dorsomedial, dorsolateral, and orbital regions of the prefrontal cortex. Moreover, during encoding of negative words, compared with positive and neutral words, VNS also modulated activity within orbitofrontal, ventromedial and polar prefrontal cortices, midcingulate cortex, and brain stem. Conclusions: Our observations show that VNS can interfere with memory of negative information, an effect that may contribute to its antidepressant role. Neuroimaging implicated regions including the ventral and medial prefrontal cortex as an underlying neural substrate.

β-adrenergic modulation of oddball responses in humans

Abstract: Detection of salient or motivationally significant stimuli is of adaptive importance. The neurophysiological correlates of this detection have been extensively studied in 'oddball' paradigms. Much theoretical data supports the role of noradrenergic systems in generating oddball responses. We combine psychopharmacology and functional neuroimaging to demonstrate modulation of neuronal responses to oddball nouns by the β-adrenergic antagonist propranolol. Critically, responses in regions implicated in oddball detection, namely right ventrolateral prefrontal cortex and temporoparietal junction (TPJ), were abolished by propranolol. Thus, oddball responses depend on modulatory adrenergic inputs, mediated via β-adrenergic receptors.

Emotion-induced retrograde amnesia varies as a function of noradrenergic-glucocorticoid activity

Abstract: Rationale Privileged episodic encoding of an aversive event often comes at a cost of neutral events flanking the aversive event, resulting in decreased episodic memory for these neutral events. This peri-emotional amnesia is amygdala-dependent and varies as a function of norepinephrine activity. However, less is known about the amnesiogenic potential of cortisol.

Enhanced emotion-induced amnesia in borderline personality disorder

Abstract: Background. Current biological concepts of borderline personality disorder (BPD) emphasize the interference of emotional hyperarousal and cognitive functions. A prototypical example is episodic memory. Pre-clinical investigations of emotion–episodic memory interactions have shown specific retrograde and anterograde episodic memory changes in response to emotional stimuli. These changes are amygdala dependent and vary as a function of emotional arousal and valence. Method. To determine whether there is amygdala hyper-responsiveness to emotional stimuli as the underlying pathological substrate of cognitive dysfunction in BPD, 16 unmedicated female patients with BPD were tested on the behavioural indices of emotion-induced amnesia and hypermnesia established in 16 healthy controls. Results. BPD patients displayed enhanced retrograde and anterograde amnesia in response to presentation of negative stimuli, while positive stimuli elicited no episodic memory-modulating effects. Conclusion. These findings suggest that an amygdala hyper-responsiveness to negative stimuli may serve as a crucial aetiological contributor to emotion-induced cognitive dysfunction in BPD.

Keynote address: revaluing the orbital prefrontal cortex.

Abstract: The importance of orbitofrontal cortex (OFC) in human behavioral regulation is no longer a matter of dispute, though its precise role remains a matter of ongoing investigation. It is ironic that this revaluation of OFC required a major departure from a historical nadir, during which it was viewed as redundant or “silent cortex,” a situation that prevailed even up to the latter half of the 20th century. The increasing wealth of data from diverse fields within neuroscience now provides an unambiguous testament to the importance of this cortical region in behavioral regulation and cognition in general.