Biomedical subjects

Raymond J Dolan

Publications and source records attributed to Raymond J Dolan.

At least 19 recordsLinked to original sources

PubMed2005

Anterior cingulate activity during error and autonomic response.

The contribution of anterior cingulate cortex (ACC) to human cognition remains unclear. The rostral (rACC) and dorsal (dACC) ACC cortex are implicated in tasks that require increased response control due to emotional and cognitive interference, respectively. However, both rACC and dACC are activated by conditions that induce changes in visceral arousal, suggesting that ACC supports a generation of integrated bodily responses. To clarify the relationship between purely cognitive and psychophysiological accounts of ACC function, we scanned 15 subjects using functional magnetic resonance imaging while they performed numerical versions of the Stroop task. To index autonomic arousal, we simultaneously measured pupil diameter. Performance errors accounted for most of the variance in a pupil-derived measure of evoked autonomic arousal. In analysis of the functional imaging data, activity within a region spanning rACC and dACC predicted trial-by-trial variation in autonomic response magnitude and was enhanced during error trials, shown using conjunction analyses. Activity within other loci within rACC predicted evoked autonomic arousal and showed sensitivity to errors but did not meet criteria for both. These data highlight the role of ACC in psychophysiological aspects of error processing and suggest that an interface exists within ACC between cognitive and biobehavioral systems in the service of response adaptation.

Adult↗

PubMed2005

Modulation of pain processing in hyperalgesia by cognitive demand.

The relationship between pain and cognitive function is of theoretical and clinical interest, exemplified by observations that attention-demanding activities reduce pain in chronically afflicted patients. Previous studies have concentrated on phasic pain, which bears little correspondence to clinical pain conditions. Indeed, phasic pain is often associated with differential or opposing effects to tonic pain in behavioral, lesion, and pharmacological studies. To address how cognitive engagement interacts with tonic pain, we assessed the influence of an attention-demanding cognitive task on pain-evoked neural responses in an experimental model of chronic pain, the capsaicin-induced heat hyperalgesia model. Using functional magnetic resonance imaging (fMRI), we show that activity in the orbitofrontal and medial prefrontal cortices, insula, and cerebellum correlates with the intensity of tonic pain. This pain-related activity in medial prefrontal cortex and cerebellum was modulated by the demand level of the cognitive task. Our findings highlight a role for these structures in the integration of motivational and cognitive functions associated with a physiological state of injury. Within the limitations of an experimental model of pain, we suggest that the findings are relevant to understanding both the neurobiology and pathophysiology of chronic pain and its amelioration by cognitive strategies.

Adult↗

PubMed2005

Noradrenergic modulation of emotion-induced forgetting and remembering.

We used a free-recall paradigm to establish a behavioral index of the retrograde and anterograde interference of emotion with episodic memory encoding. In two experiments involving 78 subjects, we show that negatively valenced items elicit retrograde amnesia, whereas positively valenced items elicit retrograde hypermnesia. These data indicate item valence is critical in determining retrograde amnesia and retrograde hypermnesia. In contrast, we show that item arousal induces an anterograde amnesic effect, consistent with the idea that a valence-evoked arousal mechanism compromises anterograde episodic encoding. Randomized double-blind administration of the beta-adrenoceptor antagonist propranolol compared with the selective norepinephrine (NE) reuptake-inhibitor reboxetine, and placebo, demonstrated that the magnitude of this emotional amnesia and hypermnesia can be upregulated and downregulated as a function of emotional arousal and central NE signaling. We conclude that a differential processing of emotional arousal and valence influences how the brain remembers and forgets.

Adrenergic Uptake Inhibitors↗

PubMed2005

Information theory, novelty and hippocampal responses: unpredicted or unpredictable?

Shannon's information theory provides a principled framework for the quantitative analysis of brain responses during the encoding and representation of event streams. In particular, entropy measures the expected uncertainty of events in a given context. This contextual uncertainty or unpredictability may, itself, be important for balancing [bottom-up] sensory information and [top-down] prior expectations during perceptual synthesis. Using event-related functional magnetic resonance imaging (fMRI), we found that the anterior hippocampus is sensitive to the entropy of a visual stimulus stream. In contrast, activity in an extensive bilateral cortico-thalamic network was dictated by the surprise or information associated with each particular stimulus. In short, we show that the probabilistic structure or context in which events occur is an important predictor of hippocampal activity.

Adult↗

PubMed2005

Dissociating intentional learning from relative novelty responses in the medial temporal lobe.

The establishment of a role for medial temporal lobe (MTL) structures in episodic memory has led to an investigative focus on the specific contributions and interactions between constituent MTL regions, including the hippocampus and surrounding medial temporal cortices. By dissociating an intentional stimulus-category learning condition from a passive viewing condition, we demonstrate, using fMRI, that novelty- and familiarity-driven responses in human anterior and posterior hippocampus, respectively, only occur during intentional learning. With increasing familiarity of stimulus-category associations, there is a shift in neuronal responses from anterior to posterior hippocampal regions. This anterior/posterior response gradient may reflect a weighting of functional hippocampal architecture related to encoding of novel and retrieval of familiar information. By contrast, perirhinal cortex is engaged by novel stimuli irrespective of task, highlighting this region as a component of a generic familiarity discrimination system. By introducing distinct stimulus types, we further demonstrate that these MTL responses are independent of stimulus complexity. Different patterns of activity for intentional learning vs. passive viewing indicate that intentional encoding/retrieval of stimulus-category associations and automatic novelty/familiarity assessment of stimuli are processed in anatomically dissociable neuronal ensembles within the MTL memory system.

Adult↗

PubMed2005

Neurophysiological correlates of increased verbal working memory in high-dissociative participants: a functional MRI study.

BACKGROUND: Dissociation, defined as a disruption in usually integrated mental functions, is found not only in DSM-IV dissociative disorders, but also in post-traumatic stress disorder and eating disorders. Dissociative phenomena are also common in the general population, and may reflect a constitutionally determined cognitive style rather than a pathological trait acquired through experiencing adverse life events. In pathological dissociation, evidence has been presented for episodic memory dysfunction. In contrast, in high-dissociative subjects increased performance has been found for episodic memory and dual task performance. These findings have been linked to changes in working memory capacity. METHOD: In the present study, the authors sought to extend these findings by using functional magnetic resonance imaging during performance of two parametric working memory tasks. We tested 21 healthy low- and high-dissociative participants. RESULTS: High-dissociative participants performed slightly better during both tasks. Imaging data showed that both groups activated similar networks for both tasks, i.e. (bilateral) dorsolateral (DL) and ventrolateral prefrontal cortex (PFC), parietal cortex, and supplementary motor area. Group x task interactions were found in the high-dissociative group in L DLPFC and L parietal cortex; in the low-dissociative group in R fusiform gyrus. The differences in the high-dissociative group were independent from performance differences, implying that high-dissociative subjects generally recruit this network to a greater extent. CONCLUSIONS: These results confirm earlier findings using a verbal WM task in high-dissociative participants, and are compatible with the conceptualization of non-pathological dissociation as an information-processing style, characterized by distinct attentional and mnemonic abilities.

Adult↗

PubMed2005

Anxiety reduction through detachment: subjective, physiological, and neural effects.

The ability to volitionally regulate emotions helps to adapt behavior to changing environmental demands and can alleviate subjective distress. We show that a cognitive strategy of detachment attenuates subjective and physiological measures of anticipatory anxiety for pain and reduces reactivity to receipt of pain itself. Using functional magnetic resonance imaging, we locate the potential site and source of this modulation of anticipatory anxiety in the medial prefrontal/anterior cingulate and anterolateral prefrontal cortex, respectively.

Adaptation, Psychological↗

PubMed2004

Amygdala activity in obsessive-compulsive disorder with contamination fear: a study with oxygen-15 water positron emission tomography.

Previous imaging studies of obsessive-compulsive symptom states have implicated frontal-striatal and limbic regions in the pathophysiology of obsessive-compulsive disorder (OCD). Functional imaging studies, however, have yielded inconsistent results, presumably due to methodological differences (patient inclusion criteria, stimulus paradigm, imaging technique, and absence of control groups). In the present study, randomized presentation of contamination-related and neutral visual stimuli was used to investigate the neurophysiological correlates of contamination fear in a group of medication-free OCD patients with washing behaviors and healthy controls. A total of 21 subjects (11 OCD patients and 10 healthy controls) were scanned using H(2)(15)O positron emission tomography (PET). Subjects were presented with pictures of clean and dirty surroundings and were requested to make indoor/outdoor decisions to control for attention differences. State anxiety and obsessionality were rated after each scan using visual analogue scales. Main effects of stimulus type (contamination vs. neutral) were found in bilateral occipital cortex in both groups. A significant group interaction effect was observed in the left amygdala reflecting enhanced activity in response to contamination stimuli in OCD patients. Sensitization effects were observed in the right amygdala in the OCD group; these paralleled an increase in levels of distress and obsessionality as well as a decrease in dorsolateral prefrontal activity. The findings of the present study are consistent with the hypothesis of decreased frontal-striatal control of limbic structures, specifically the amygdala, resulting in an inadequate fear response in OCD patients with contamination fear.

Adult↗

PubMed2004

Neurophysiological correlates of habituation during exposure in spider phobia.

Imaging studies using symptom-provocation paradigms in specific phobia have yielded contradictory results, possibly reflecting a failure to account for habituation processes. Given that a single session of exposure in vivo can result in significant improvement in specific phobia, we used prolonged exposure to phobic stimuli to identify CNS regions showing habituation. Eighteen subjects (12 with spider phobia, 6 healthy controls) underwent H(2)(15)O-positron emission tomography while being continuously presented with pictures of spiders or butterflies. Results showed main effects (spiders>butterflies) in the phobia group in the left fusiform gyrus (FG) and the right parahippocampal gyrus (PHG), with bilateral perirhinal cortex and right limbic areas approaching significance. Group x condition effects were found in the right amygdala and PHG. During spider scans, large habituation effects were observed in the anterior medial temporal lobe (MTL) bilaterally. Regression analyses demonstrated that state anxiety was correlated with activity in left amygdala, bilateral perirhinal cortex, right FG, and periaquaductal grey; by contrast, phobic fear was only associated with right-sided hippocampal activity. We conclude that prolonged exposure to phobic stimuli is associated with a significant decrease in bilateral anterior MTL regional cerebral blood flow. Right anterior MTL, identified when comparing phobic vs. neutral stimuli and habituation to phobic vs. neutral stimuli in the phobia group, implicates this region in phobic fear. Analyses of covariance suggest a further functional segregation with state anxiety being linked to enhanced activity in amygdala, perirhinal cortex, and tegmentum, and phobic fear with enhanced right hippocampal activity, suggesting a neuroanatomical differentiation between emotional-vegetative and cognitive aspects of (phobic) fear.

Adult↗

PubMed2004

Morphing Marilyn into Maggie dissociates physical and identity face representations in the brain.

How the brain represents different aspects of faces remains controversial. Here we presented subjects with stimuli drawn from morph continua between pairs of famous faces. In the paired presentations, a second face could be identical to the first, could share perceived identity but differ physically (30% along the morph continuum), or could differ physically by the same distance along the continuum (30%) but in the other direction. We show that, behaviorally, subjects are more likely to classify face pairs in the third paired presentation as different and that this effect is more pronounced for subjects who are more familiar with the faces. In functional magnetic resonance imaging (fMRI), inferior occipital gyrus (IOG) shows sensitivity to physical rather than to identity changes, whereas right fusiform gyrus (FFG) shows sensitivity to identity rather than to physical changes. Bilateral anterior temporal regions show sensitivity to identity change that varies with the subjects' pre-experimental familiarity with the faces. These findings provide neurobiological support for a hierarchical model of face perception.

Adult↗

PubMed2004

Activity in the human brain predicting differential heart rate responses to emotional facial expressions.

The James-Lange theory of emotion proposes that automatically generated bodily reactions not only color subjective emotional experience of stimuli, but also necessitate a mechanism by which these bodily reactions are differentially generated to reflect stimulus quality. To examine this putative mechanism, we simultaneously measured brain activity and heart rate to identify regions where neural activity predicted the magnitude of heart rate responses to emotional facial expressions. Using a forewarned reaction time task, we showed that orienting heart rate acceleration to emotional face stimuli was modulated as a function of the emotion depicted. The magnitude of evoked heart rate increase, both across the stimulus set and within each emotion category, was predicted by level of activity within a matrix of interconnected brain regions, including amygdala, insula, anterior cingulate, and brainstem. We suggest that these regions provide a substrate for translating visual perception of emotional facial expression into differential cardiac responses and thereby represent an interface for selective generation of visceral reactions that contribute to the embodied component of emotional reaction.

Adult↗

PubMed2004

Distant influences of amygdala lesion on visual cortical activation during emotional face processing.

Emotional visual stimuli evoke enhanced responses in the visual cortex. To test whether this reflects modulatory influences from the amygdala on sensory processing, we used event-related functional magnetic resonance imaging (fMRI) in human patients with medial temporal lobe sclerosis. Twenty-six patients with lesions in the amygdala, the hippocampus or both, plus 13 matched healthy controls, were shown pictures of fearful or neutral faces in task-releant or task-irrelevant positions on the display. All subjects showed increased fusiform cortex activation when the faces were in task-relevant positions. Both healthy individuals and those with hippocampal damage showed increased activation in the fusiform and occipital cortex when they were shown fearful faces, but this was not the case for individuals with damage to the amygdala, even though visual areas were structurally intact. The distant influence of the amygdala was also evidenced by the parametric relationship between amygdala damage and the level of emotional activation in the fusiform cortex. Our data show that combining the fMRI and lesion approaches can help reveal the source of functional modulatory influences between distant but interconnected brain regions.

Adult↗

PubMed2004

Mental stress and sudden cardiac death: asymmetric midbrain activity as a linking mechanism.

Patients with specific neurological, psychiatric or cardiovascular conditions are at enhanced risk of cardiac arrhythmia and sudden death. The neurogenic mechanisms are poorly understood. However, in many cases, stress may precipitate cardiac arrhythmia and sudden death in vulnerable patients, presumably via centrally driven autonomic nervous system responses. From a cardiological perspective, the likelihood of arrhythmia is strongly associated with abnormalities in electrical repolarization (recovery) of the heart muscle after each contraction. Inhomogeneous and asymmetric repolarization, reflected in ECG T-wave abnormalities, is associated with a greatly increased risk of arrhythmia, i.e. a proarrhythmic state. We therefore undertook a study to identify the brain mechanisms by which stress can induce cardiac arrhythmia through efferent autonomic drive. We recruited a typical group of 10 out-patients attending a cardiological clinic. We simultaneously measured brain activity, using H2(15)O PET, and the proarrhythmic state of the heart, using ECG, during mental and physical stress challenges and corresponding control conditions. Proarrhythmic changes in the heart were quantified from two ECG-derived measures of repolarization inhomogeneity and were related to changes in magnitude and lateralization of regional brain activity reflected in regional cerebral blood flow. Across the patient group, we observed a robust positive relationship between right-lateralized asymmetry in midbrain activity and proarrhythmic abnormalities of cardiac repolarization (apparent in two independent ECG measures) during stress. This association between stress-induced lateralization of midbrain activity and enhanced arrhythmic vulnerability provides empirical support for a putative mechanism for stress-induced sudden death, wherein lateralization of central autonomic drive during stress results in imbalanced activity in right and left cardiac sympathetic nerves. A right-left asymmetry in sympathetic drive across the surface of the heart disrupts the electrophysiological homogeneity of ventricular repolarization, predisposing to arrhythmia. Our findings highlight a proximal brain basis for stress-induced cardiac arrhythmic vulnerability.

Aged↗

PubMed2004

Pre-operative verbal memory fMRI predicts post-operative memory decline after left temporal lobe resection.

Functional MRI (fMRI) of cognitive tasks depends on technology widely available in the clinical sphere, but has yet to show a role in the investigation of patients. We report here the first demonstration of a clinically valuable role for cognitive fMRI. Temporal lobe epilepsy (TLE) is commonly caused by hippocampal sclerosis and is frequently resistant to drug treatment. Surgical resection of the left hippocampus in this setting can cure seizures, but may produce significant verbal memory decline, which is hard to predict. We report 10 right-handed TLE patients with left hippocampal sclerosis who underwent left hippocampal resection. We compared currently used data for the prediction of post-operative verbal memory decline in such patients with a novel fMRI assessment of verbal memory encoding. Multiple regression analyses showed that fMRI provided the strongest independent predictor of memory outcome after surgery. At the individual subject level, the fMRI data had high positive predictive value for memory decline.

Adult↗

PubMed2004

Attentional load and sensory competition in human vision: modulation of fMRI responses by load at fixation during task-irrelevant stimulation in the peripheral visual field.

Perceptual suppression of distractors may depend on both endogenous and exogenous factors, such as attentional load of the current task and sensory competition among simultaneous stimuli, respectively. We used functional magnetic resonance imaging (fMRI) to compare these two types of attentional effects and examine how they may interact in the human brain. We varied the attentional load of a visual monitoring task performed on a rapid stream at central fixation without altering the central stimuli themselves, while measuring the impact on fMRI responses to task-irrelevant peripheral checkerboards presented either unilaterally or bilaterally. Activations in visual cortex for irrelevant peripheral stimulation decreased with increasing attentional load at fixation. This relative decrease was present even in V1, but became larger for successive visual areas through to V4. Decreases in activation for contralateral peripheral checkerboards due to higher central load were more pronounced within retinotopic cortex corresponding to 'inner' peripheral locations relatively near the central targets than for more eccentric 'outer' locations, demonstrating a predominant suppression of nearby surround rather than strict 'tunnel vision' during higher task load at central fixation. Contralateral activations for peripheral stimulation in one hemifield were reduced by competition with concurrent stimulation in the other hemifield only in inferior parietal cortex, not in retinotopic areas of occipital visual cortex. In addition, central attentional load interacted with competition due to bilateral versus unilateral peripheral stimuli specifically in posterior parietal and fusiform regions. These results reveal that task-dependent attentional load, and interhemifield stimulus-competition, can produce distinct influences on the neural responses to peripheral visual stimuli within the human visual system. These distinct mechanisms in selective visual processing may be integrated within posterior parietal areas, rather than earlier occipital cortex.

Adult↗

PubMed2004

Human orbitofrontal cortex mediates extinction learning while accessing conditioned representations of value.

In extinction, an animal learns that a previously conditioned stimulus (CS+) no longer predicts delivery of a salient reinforcer (unconditioned stimulus, UCS). Rodent studies indicate that extinction relies on amygdala-prefrontal interactions and involves formation of memories that inhibit, without actually erasing, the original conditioning trace. Whether extinction learning in humans follows similar neurobiological principles is unknown. We used functional magnetic resonance imaging to measure human brain activity evoked during olfactory aversive conditioning and extinction learning. Neural responses in orbitofrontal cortex and amygdala were preferentially enhanced during extinction, suggesting potential cross-species preservation of learning mechanisms that oppose conditioning. Moreover, by manipulating UCS aversiveness via reinforcer inflation, we showed that a CS+ retains access to representations of UCS value in distinct regions of ventral prefrontal cortex, even as extinction proceeds.

Adolescent↗

PubMed2004

Abnormal ventral frontal response during performance of an affective go/no go task in patients with mania.

BACKGROUND: Patients with mania show a behavioral bias toward positive information in an emotional go/no go task. This is the converse of the bias toward negative information seen in unipolar depression that we have recently related to the abnormal function of ventral and medial prefrontal cortices (PFCs). The aim of this study was to investigate the neuronal basis of the bias toward positive information in manic patients. METHODS: During performance of an emotional go/no go task using functional magnetic resonance imaging, 8 manic patients and 11 healthy controls were scanned. The task allowed comparison between neural response to happy, sad, and neutral words in the context of these words being either targets or distracters. RESULTS: Manic patients showed attenuated orbitofrontal response when all the semantic conditions were compared with a control condition; however, they showed an enhanced response of the left ventrolateral PFC to emotional relative to neutral targets, as well as enhanced ventral and medial prefrontal response to emotional, particularly happy, distracters. CONCLUSIONS: These results suggest a critical role for ventral and medial dysfunction in the pathology of mania, which might underpin aspects of cognitive and clinical symptomatology.

Adolescent↗

PubMed2004

Temporal difference models describe higher-order learning in humans.

The ability to use environmental stimuli to predict impending harm is critical for survival. Such predictions should be available as early as they are reliable. In pavlovian conditioning, chains of successively earlier predictors are studied in terms of higher-order relationships, and have inspired computational theories such as temporal difference learning. However, there is at present no adequate neurobiological account of how this learning occurs. Here, in a functional magnetic resonance imaging (fMRI) study of higher-order aversive conditioning, we describe a key computational strategy that humans use to learn predictions about pain. We show that neural activity in the ventral striatum and the anterior insula displays a marked correspondence to the signals for sequential learning predicted by temporal difference models. This result reveals a flexible aversive learning process ideally suited to the changing and uncertain nature of real-world environments. Taken with existing data on reward learning, our results suggest a critical role for the ventral striatum in integrating complex appetitive and aversive predictions to coordinate behaviour.

Conditioning, Classical↗