Rebecca Elliott

Neuronal correlates of theory of mind and empathy: A functional magnetic resonance imaging study in a nonverbal task

Theory of Mind (ToM), the ability to attribute mental states to others, and empathy, the ability to infer emotional experiences, are important processes in social cognition. Brain imaging studies in healthy subjects have described a brain system involving medial prefrontal cortex, superior temporal sulcus and temporal pole in ToM processing. Studies investigating networks associated with empathic responding also suggest involvement of temporal and frontal lobe regions. In this fMRI study, we used a cartoon task derived from Sarfati et al. (1997) [Sarfati, Y., Hardy-Bayle, M.C., Besche, C., Widlocher, D. 1997. Attribution of intentions to others in people with schizophrenia: a non-verbal exploration with comic strips. Schizophrenia Research 25, 199-209.]with both ToM and empathy stimuli in order to allow comparison of brain activations in these two processes. Results of 13 right-handed, healthy, male volunteers were included. Functional images were acquired using a 1.5 T Phillips Gyroscan. Our results confirmed that ToM and empathy stimuli are associated with overlapping but distinct neuronal networks. Common areas of activation included the medial prefrontal cortex, temporoparietal junction and temporal poles. Compared to the empathy condition, ToM stimuli revealed increased activations in lateral orbitofrontal cortex, middle frontal gyrus, cuneus and superior temporal gyrus. Empathy, on the other hand, was associated with enhanced activations of paracingulate, anterior and posterior cingulate and amygdala. We therefore suggest that ToM and empathy both rely on networks associated with making inferences about mental states of others. However, empathic responding requires the additional recruitment of networks involved in emotional processing. These results have implications for our understanding of disorders characterized by impairments of social cognition, such as autism and psychopathy.

Response inhibition and impulsivity: an fMRI study

Aggressive, suicidal and violent behaviour have been associated with impulsive personality and difficulty in inhibiting responses. We used functional magnetic resonance imaging (fMRI) of the whole brain to examine the neural correlates of response inhibition in 19 normal subjects as they performed a Go/NoGo task. Subjects completed Eysencks Impulsivity Scale, Barratts Impulsivity Scale (BIS) and behavioural impulsivity tasks. Associations between blood oxygen level dependent (BOLD) response, trait impulsivity, task performance and National Adult Reading Test (NART) IQ were investigated. Neural response during response inhibition was most prominent in the right lateral orbitofrontal cortex. Responses were also seen in superior temporal gyrus, medial orbitofrontal cortex, cingulate gyrus, and inferior parietal lobule, predominantly on the right side. Subjects with greater scores on impulsivity scales and who made more errors had greater activation of paralimbic areas during response inhibition, while less impulsive individuals and those with least errors activated higher order association areas. Exploratory factor analysis of orbital activations, personality measures and errors of commission did not reveal a unitary dimension of impulsivity. However, the strong association between posterior orbital activation and Eysencks impulsivity score on a single factor suggests that greater engagement of right orbitofrontal cortex was needed to maintain behavioural inhibition in impulsive individuals. Lower IQ was more important than impulsivity scores in determining errors of commission during the task. Neuroimaging of brain activity during the Go/NoGo task may be useful in understanding the functional neuroanatomy and associated neurochemistry of response inhibition. It may also allow study of the effects of physical and psychological interventions on response inhibition in clinical conditions such as antisocial personality disorder.

Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype

A key challenge in radiotherapy is to maximize radiation doses to cancer cells while minimizing damage to surrounding healthy tissue. As severe toxicity in a minority of patients limits the doses that can be safely given to the majority, there is interest in developing a test to measure an individuals radiosensitivity before treatment. Variation in sensitivity to radiation is an inherited genetic trait and recent progress in genotyping raises the possibility of genome-wide studies to characterize genetic profiles that predict patient response to radiotherapy.

The Effect of Citalopram Pretreatment on Neuronal Responses to Neuropsychological Tasks in Normal Volunteers: An fMRI Study

Changes in serotonin neurotransmission have also been implicated in the etiology and treatment of impulse control disorders, depression, and anxiety. We have investigated the effect of enhancing serotonin function on fundamental brain processes that we have proposed are abnormal in these disorders. In all, 12 male volunteers received citalopram (7.5 mg intravenously) and placebo pretreatment in a single-blind crossover design before undertaking Go/No-go, Loss/No-loss, and covert (aversive) face emotion recognition tasks during functional magnetic resonance imaging (fMRI). Blood oxygenation level dependent responses were analyzed using Statistical Parametric Mapping (SPM2). The tasks activated prefrontal and subcortical regions generally consistent with literature with lateral orbitofrontal cortex (BA47) common to the three tasks. Citalopram pretreatment enhanced the right BA47 responses to the No-go condition, but attenuated this response to aversive faces. Attenuations were seen following citalopram in the medial orbitofrontal (BA11) responses to the No-go and No-loss (ie relative reward compared with Loss) conditions. The right amygdala response to aversive faces was attenuated by citalopram. These results support the involvement of serotonin in modulating basic processes involved in psychiatric disorders but argue for a process-specific, rather than general effect. The technique of combining drug challenge with fMRI (pharmacoMRI) has promise for investigating human psychiatric disorders.

Attention to pain localization and unpleasantness discriminates the functions of the medial and lateral pain systems.

Functional imaging studies have identified a matrix of structures in the brain that respond to noxious stimuli. Within this matrix, a division of function between sensory‐discriminative and affective responses has so far been demonstrated by manipulating either pain intensity or unpleasantness under hypnosis in two different normal volunteer groups studied on separate occasions. Our study used positron emission tomography (PET) to demonstrate this division of function under more natural conditions in a healthy group of volunteers, using a CO2 laser to provide nociceptive stimuli that selectively activate A‐delta and C‐fibres without contamination by touch sensations. We measured the differential cerebral responses to noxious and innocuous laser stimuli during conditions of selective attention to either the unpleasantness or location of the stimuli. Attention to location increased responses in the contralateral (right) primary somatosensory and inferior parietal cortices. This result implies that these components of the lateral pain system are concerned mainly with the localization of pain. In contrast, attention to unpleasantness increased responses in bilateral perigenual cingulate and orbitofrontal cortices, contralateral (right) amygdala, ipsilateral (left) hypothalamus, posterior insula, M1 and frontal pole. These areas comprise key components of the medial pain and neuroendocrine systems and the results suggest that they have a role in the affective response to pain. Our results indicate the importance of attentional effects on the pattern of nociceptive processing in the brain. They also provide the first clear demonstration, within a single experiment, of a major division of function within the neural pain matrix.

Cognitive Mechanisms of Treatment in Depression

Cognitive abnormalities are a core feature of depression, and biases toward negatively toned emotional information are common, but are they a cause or a consequence of depressive symptoms? Here, we propose a ‘cognitive neuropsychological’ model of depression, suggesting that negative information processing biases have a central causal role in the development of symptoms of depression, and that treatments exert their beneficial effects by abolishing these biases. We review the evidence pertaining to this model: briefly with respect to currently depressed patients, and in more detail with respect to individuals at risk for depression and the effects of antidepressant treatments. As well as being present in currently depressed individuals, negative biases are detectable in those vulnerable for depression due to neuroticism, genetic risk, or previous depressive illness. Recent evidence provides strong support for the notion that both antidepressant drugs and psychological therapies modify negative biases, providing a common mechanism for understanding treatments for depression. Intriguingly, it may even be possible to predict which patients will benefit most from which treatments on the basis of neural responses to negative stimuli. However, further research is required to ascertain whether negative processing biases will be useful in predicting, detecting, and treating depression, and hence in preventing a chronic, relapsing course of illness.

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.

Selective attention to emotional stimuli in a verbal go/no-go task: An fMRI study

Tasks requiring subjects to attend emotional attributes of words have been used to study mood-congruent information processing biases in anxiety and affective disorders. In this study we adapted an emotional go/no-go task, for use with fMRI to assess the neural substrates of focusing on emotional attributes of words in normal subjects. The key findings were that responding to targets defined on the basis of meaning of words compared to targets defined on the basis of perceptual features was associated with response in inferior frontal gyrus and dorsal anterior cingulate. Further, selecting emotional targets, whether happy or sad, was associated with enhanced response in the subgenual cingulate, while happy targets elicited enhanced neural response in ventral anterior cingulate. These findings reaffirm the importance of medial prefrontal regions in normal emotional processing.

Affective cognition and its disruption in mood disorders.

In this review, we consider affective cognition, responses to emotional stimuli occurring in the context of cognitive evaluation. In particular, we discuss emotion categorization, biasing of memory and attention, as well as social/moral emotion. We discuss limited neuropsychological evidence suggesting that affective cognition depends critically on the amygdala, ventromedial frontal cortex, and the connections between them. We then consider neuroimaging studies of affective cognition in healthy volunteers, which have led to the development of more sophisticated neural models of these processes. Disturbances of affective cognition are a core and specific feature of mood disorders, and we discuss the evidence supporting this claim, both from behavioral and neuroimaging perspectives. Serotonin is considered to be a key neurotransmitter involved in depression, and there is a considerable body of research exploring whether serotonin may mediate disturbances of affective cognition. The final section presents an overview of this literature and considers implications for understanding the pathophysiology of mood disorder as well as developing and evaluating new treatment strategies.

The neuropsychological profile in unipolar depression

There is a wealth of empirical data pertaining to the issue of neuropsychological impairment in depression. However, a coherent and comprehensive framework for understanding the disorder remains elusive. This review will briefly consider some of the important issues on which recent research has focused. It would be premature to derive firm conclusions in an area characterized by considerable confusion, so the aim of this review is to highlight the key areas that must be addressed. Three distinct questions are considered. The first concerns the neuropsychological specificity of the deficits associated with depression; whether they represent selective deficits or a more general profile of impairment. The second question is to determine how cognitive deficits might relate to clinical and demographic factors, including symptom severity, hospitalization, medication and ageing. Finally, a comprehensive theory of depression must also relate impairments to neuropathology, and evidence is now available from imaging studies that have attempted to elucidate neural substrates of neuropsychological deficits.