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Biomedical subjects

R J Dolan

Publications and source records attributed to R J Dolan.

At least 37 records · Page 2Linked to original sources

An emotion-induced retrograde amnesia in humans is amygdala- and beta-adrenergic-dependent.

The influence of emotion on human memory is associated with two contradictory effects in the form of either emotion-induced enhancements or decrements in memory. In a series of experiments involving single word presentation, we show that enhanced memory for emotional words is strongly coupled to decrements in memory for items preceding the emotional stimulus, an effect that is more pronounced in women. These memory effects would appear to depend on a common neurobiological substrate, in that enhancements and decrements are reversed by propranolol, a beta-adrenergic antagonist, and abolished by selective bilateral amygdala damage. Thus, our findings suggest that amygdala-dependent beta-adrenergic modulation of episodic encoding has costs as well as benefits.

Adult↗

Neuronal correlates of familiarity-driven decisions in artificial grammar learning.

It has been proposed on the basis of behavioural data that grammaticality judgments in implicit artificial grammar learning paradigms are largely driven by priming based on fragment familiarity. A prediction that follows from this account is that neural deactivation, a common correlate of repetition priming, should be observed for grammatical compared to ungrammatical stimuli. We conducted an event-related fMRI study to investigate neuronal correlates of such fragment-based priming. In a study phase, participants performed a short-term memory task on a series of strings of pseudofont characters. Scanning was performed in a subsequent test phase in which participants classified new strings as either grammatical or ungrammatical. Test strings differed systematically from training strings in terms of exemplar and fragment similarity. Behaviourally, participants classified strings as grammatical based on fragment familiarity. Differential activity was evident during string classification as reduced activity in left lateral occipital complex and bilateral lingual gyri for strings with high fragment familiarity compared to strings with low fragment familiarity. Thus, consistent with the hypothesis, neuronal facilitation in extrastriate occipital regions may constitute one basis of implicit grammaticality decisions based on fragment priming.

Adult↗

Beauty in a smile: the role of medial orbitofrontal cortex in facial attractiveness.

The attractiveness of a face is a highly salient social signal, influencing mate choice and other social judgements. In this study, we used event-related functional magnetic resonance imaging (fMRI) to investigate brain regions that respond to attractive faces which manifested either a neutral or mildly happy face expression. Attractive faces produced activation of medial orbitofrontal cortex (OFC), a region involved in representing stimulus-reward value. Responses in this region were further enhanced by a smiling facial expression, suggesting that the reward value of an attractive face as indexed by medial OFC activity is modulated by a perceiver directed smile.

Adult↗

Common and distinct neural responses during direct and incidental processing of multiple facial emotions.

Whether common or distinct neural systems underpin perception of different emotions and the degree to which these systems are automatically engaged during emotional perception are unresolved. We performed an event-related fMRI experiment in which subjects viewed morphed emotional faces displaying low or high intensities of disgust, fear, happiness, or sadness under two task conditions. The amygdala and fusiform cortex responded to high-intensity expressions of all emotions, independent of task. Right superior temporal sulcus showed an additive effect of the emotion-directed task and high-intensity emotion. Ventromedial prefrontal and somatosensory cortices, regions implicated in providing representations of somatic states, showed enhanced activity during explicit emotional judgments. We failed to find predicted differences between emotions. The results suggest that amygdala contributes to task-independent perceptual processing of a range of emotions. We interpret ventromedial prefrontal and somatosensory cortex activations as evidence that these regions contribute to explicit emotion processing through linking emotion perception with representations of somatic states previously engendered by emotions.

Adult↗

Amygdala automaticity in emotional processing.

The question addressed in this paper is whether the human amygdala processes threat-related stimuli independent of selective attention. This is considered from a functional neuroimaging perspective, describing studies in normal volunteers and patients with brain lesions. The conclusion is that the evidence for such automaticity is strong, indicating that important distinctions exist between emotion and other forms of cognition.

Amygdala↗

Emotion, cognition, and behavior.

Emotion is central to the quality and range of everyday human experience. The neurobiological substrates of human emotion are now attracting increasing interest within the neurosciences motivated, to a considerable extent, by advances in functional neuroimaging techniques. An emerging theme is the question of how emotion interacts with and influences other domains of cognition, in particular attention, memory, and reasoning. The psychological consequences and mechanisms underlying the emotional modulation of cognition provide the focus of this article.

Attention↗

Dissociable human perirhinal, hippocampal, and parahippocampal roles during verbal encoding.

The precise contribution of perirhinal cortex to human episodic memory is uncertain. Human intracranial recordings highlight a role in successful episodic memory encoding, but encoding-related perirhinal activation has not been observed with functional imaging. By adapting functional magnetic resonance imaging scanning parameters to maximize sensitivity to medial temporal lobe activity, we demonstrate that left perirhinal and hippocampal responses during word list encoding are greater for subsequently recalled than forgotten words. Although perirhinal responses predict memory for all words, successful encoding of initial words in a list, demonstrating a primacy effect, is associated with parahippocampal and anterior hippocampal activation. We conclude that perirhinal cortex and hippocampus participate in successful memory encoding. Encoding-related parahippocampal and anterior hippocampal responses for initial, remembered words most likely reflects enhanced attentional orienting to these positionally distinctive items.

Adult↗

Human amygdala responses to fearful eyes.

Fearful facial expressions evoke increased neural responses in human amygdala. We used event-related fMRI to investigate whether eye or mouth components of a fearful face are critical in evoking this increased amygdala activity. In addition to prototypical fearful (FF) and neutral (NN) faces, subjects viewed two types of chimerical face: fearful eyes combined with a neutral mouth (FN), and neutral eyes combined with a fearful mouth (NF). FE faces evoked specific responses in left anterior amygdala. FN faces evoked responses in bilateral posterior amygdala and superior colliculus. Responses in right amygdala, superior colliculus, and pulvinar exhibited significant time x condition interactions with respect to faces with fearful eyes (FF, FN) vs neutral eyes (NF, NN). These data indicate that fearful eyes alone are sufficient to evoke increased amygdala activity. In addition, however, left amygdala displayed discriminatory responses to fearful eyes in different configural contexts (i.e., in FF and FN faces). These results suggest, therefore, that human amygdala responds to both feature-specific and configural aspects of fearful facial expressions.

Adult↗

Neural response to emotional faces with and without awareness: event-related fMRI in a parietal patient with visual extinction and spatial neglect.

This study examined whether differential neural responses are evoked by emotional stimuli with and without conscious perception, in a patient with visual neglect and extinction. Stimuli were briefly shown in either right, left, or both fields during event-related fMRI. On bilateral trials, either a fearful or neutral left face appeared with a right house, and it could either be extinguished from awareness or perceived. Seen faces in left visual field (LVF) activated primary visual cortex in the damaged right-hemisphere and bilateral fusiform gyri. Extinguished left faces increased activity in striate and extrastriate cortex, compared with right houses only. Critically, fearful faces activated the left amygdala and extrastriate cortex both when seen and when extinguished; as well as bilateral orbitofrontal and intact right superior parietal areas. Comparison of perceived versus extinguished faces revealed no difference in amygdala for fearful faces. Conscious perception increased activity in fusiform, parietal and prefrontal areas of the left-hemisphere, irrespective of emotional expression; while a differential emotional response to fearful faces occurring specifically with awareness was found in bilateral parietal, temporal, and frontal areas. These results demonstrate that amygdala and orbitofrontal cortex can be activated by emotional stimuli even without awareness after parietal damage; and that substantial unconscious residual processing can occur within spared brain areas well beyond visual cortex, despite neglect and extinction.

Aged↗

Automatic and intentional brain responses during evaluation of trustworthiness of faces.

Successful social interaction partly depends on appraisal of others from their facial appearance. A critical aspect of this appraisal relates to whether we consider others to be trustworthy. We determined the neural basis for such trustworthiness judgments using event-related functional magnetic resonance imaging. Subjects viewed faces and assessed either trustworthiness or age. In a parametric factorial design, trustworthiness ratings were correlated with BOLD signal change to reveal task-independent increased activity in bilateral amygdala and right insula in response to faces judged untrustworthy. Right superior temporal sulcus (STS) showed enhanced signal change during explicit trustworthiness judgments alone. The findings extend a proposed model of social cognition by highlighting a functional dissociation between automatic engagement of amygdala versus intentional engagement of STS in social judgment.

Adolescent↗

Multiple levels of visual object constancy revealed by event-related fMRI of repetition priming.

We conducted two event-related functional magnetic resonance imaging (fMRI) experiments to investigate the neural substrates of visual object recognition in humans. We used a repetition-priming method with visual stimuli recurring at unpredictable intervals, either with the same appearance or with changes in size, viewpoint or exemplar. Lateral occipital and posterior inferior temporal cortex showed lower activity for repetitions of both real and non-sense objects; fusiform and left inferior frontal regions showed decreases for repetitions of only real objects. Repetition of different exemplars with the same name affected only the left inferior frontal cortex. Crucially, priming-induced decreases in activity of the right fusiform cortex depended on whether the three-dimensional objects were repeated with the same viewpoint, regardless of whether retinal image size changed; left fusiform decreases were independent of both viewpoint and size. These data show that dissociable subsystems in ventral visual cortex maintain distinct view-dependent and view-invariant object representations.

Adult↗

Effects of cholinergic enhancement on conditioning-related responses in human auditory cortex.

It has previously been shown that cholinergic blockade attenuates conditioning-related neuronal responses in human auditory cortex. The present study was conducted to investigate the effect of cholinergic enhancement on such experience-dependent cortical responses. The cholinesterase inhibitor physostigmine, or a placebo control, were continuously infused into healthy young volunteers, during differential aversive conditioning whilst brain activity was measured using event-related functional magnetic resonance imaging (fMRI). Volunteers were presented with two tones, one of which (CS+) was conditioned by pairing with an electrical shock whereas the other was always presented without the shock (CS-). Conditioning-related activations, expressed as an enhanced blood oxygenation level dependent (BOLD) response to the salient CS+, were evident in left auditory cortex under placebo but not under physostigmine. This absence of conditioning-related activations under physostigmine was due to enhanced responses to the CS- under physostigmine as compared to placebo. We suggest that an overactive cholinergic system leads to increased processing of behaviourally irrelevant stimuli and thus attenuates differential conditioning-related cortical activations.

Acetylcholine↗

An fMRI study of intentional and unintentional (embarrassing) violations of social norms.

The aim of this investigation was to identify neural systems supporting the processing of intentional and unintentional transgressions of social norms. Using event-related fMRI, we addressed this question by comparing neural responses to stories describing normal behaviour, embarrassing situations or violations of social norms. Processing transgressions of social norms involved systems previously reported to play a role in representing the mental states of others, namely medial prefrontal and temporal regions. In addition, the processing of transgressions of social norms involved systems previously found to respond to aversive emotional expressions (in particular angry expressions); namely lateral orbitofrontal cortex (Brodmann area 47) and medial prefrontal cortex. The observed responses were similar for both intentional and unintentional social norm violations, albeit more pronounced for the intentional norm violations. These data suggest that social behavioural problems in patients with frontal lobe lesions or fronto-temporal dementia may be a consequence of dysfunction within the systems identified in light of their possible role in processing whether particular social behaviours are, or are not, appropriate.

Adult↗

Face repetition effects in implicit and explicit memory tests as measured by fMRI.

Recent parallels between neurophysiological and neuroimaging findings suggest that repeated stimulus processing produces decreased responses in brain regions associated with that processing--a 'repetition suppression' effect. In the present study, volunteers performed two tasks on repeated presentation of famous and unfamiliar faces during functional magnetic resonance imaging (fMRI). In the implicit task, they made fame-judgements (regardless of repetition); in the explicit task, they made episodic recognition judgements (regardless of familiarity). Only in the implicit task was repetition suppression observed: for famous faces in a right lateral fusiform region, and for both famous and unfamiliar faces in a left inferior occipital region. Repetition suppression is therefore not an automatic consequence of repeated perceptual processing of stimuli.

Adult↗

Functional magnetic resonance imaging of proactive interference during spoken cued recall.

Though lesions to frontal cortex can increase susceptibility to interference from previously established but irrelevant memories ("proactive interference"), the specific regions underlying this problem are difficult to determine because the lesions are typically large and heterogeneous. We used event-related functional magnetic resonance imaging to investigate proactive interference in healthy volunteers performing an "AB-AC" paired-associate cued-recall paradigm. At Study, participants intentionally encoded semantically related visual word pairs, which were changed three times (high interference), repeated three times (low interference), or presented only once. At Test, participants were presented with the first word of each pair and attempted to recall its most recent associate from the Study phase. To overcome the problem of image artifacts caused by speech-related head motion, we cued speech during a gap between image acquisitions. Regions in left inferior frontal cortex and bilateral frontopolar cortex showed interference effects during both Study and Test. The pattern of responses in these regions differed, however. Left inferior frontal regions showed mainly reduced responses associated with low interference, whereas frontopolar regions showed mainly increased responses associated with high interference. When incorrect as well as correct trials were analyzed at Test, additional activation associated with high interference was observed in right dorsolateral prefrontal cortex. These data suggest that distinct regions within prefrontal cortex subserve different functions in the presence of proactive interference during cued recall.

Artifacts↗

A novel presenilin mutation (M233V) causing very early onset Alzheimer's disease with Lewy bodies.

Presenilin 1 mutations are the major cause of autosomal dominant Alzheimer's disease: here we identify a new missense mutation causing a methionine to valine change at codon 233. This codon is homologous to a pathogenic presenilin 2 mutation with the same base change (ATG to GTG) and amino acid change (M239V). This mutation causes disease with an exceptionally early onset age (approximately 30 years) in which pathological examination shows extensive Lewy bodies as well as plaques and tangles.

Adult↗

Modulation of auditory neural responses by a visual context in human fear conditioning.

Responses to a stimulus signaling danger depend not only on the nature of that stimulus, but also on the context in which it is presented. A large body of work has been conducted in experimental animals investigating the neural correlates of contextual modulation of fear responses. However, much less is known about this process in humans. In this study we used functional MRI in a fear conditioning paradigm to explore this phenomenon. Responses to acoustic conditioned stimuli in auditory cortex were modulated by the presence of a visual context which signaled the likelihood of receiving an aversive unconditioned stimulus. Furthermore, the presence of the aversive visual context was associated with enhanced activity in parietal cortex, which may reflect an increase in attention to the presence of environmental threat stimuli.

Acoustic Stimulation↗

Reward value of attractiveness and gaze.

Faces are visual objects in our environment that provide strong social cues, with the eyes assuming particular importance. Here we show that the perceived attractiveness of an unfamiliar face increases brain activity in the ventral striatum of the viewer when meeting the person's eye, and decreases activity when eye gaze is directed away. Depending on the direction of gaze, attractiveness can thus activate dopaminergic regions that are strongly linked to reward prediction, indicating that central reward systems may be engaged during the initiation of social interactions.

Basal Ganglia↗