Deriving meaning: Distinct neural mechanisms for metaphoric, literal, and non-meaningful sentences.

In this study, we used a novel cognitive paradigm and event-related functional magnetic resonance imaging (ER-fMRI) to investigate the neural substrates involved in processing three different types of sentences. Participants read either metaphoric (Some surgeons are butchers), literal (Some surgeons are fathers), or non-meaningful sentences (Some surgeons are shelves) and had to decide whether they made sense or not. We demonstrate that processing of the different sentence types relied on distinct neural mechanisms. Activation of the left inferior frontal gyrus (LIFG), BA 47, was shared by both non-meaningful and metaphoric sentences but not by literal sentences. Furthermore, activation of the left thalamus appeared to be specifically involved in deriving meaning from metaphoric sentences despite lack of reaction times differences between literals and metaphors. We assign this to the ad hoc concept construction and open-endedness of metaphoric interpretation. In contrast to previous studies, our results do not support the view the right hemispheric is specifically involved in metaphor comprehension.

Empathy and enduring depersonalization: the role of self-related processes.

Empathy has two key components: affective and cognitive. It relies on "embodied" processes such as the generation, representation and perception of feeling states. People diagnosed with Depersonalization Disorder (DPD) report disturbances in affective experience, such as emotional numbing, alongside aberrations in "body image" such as increased self-focus and feelings of "disembodiment". DPD therefore provides a test bed for the role of such self-related processes in empathy. We tested 16 participants diagnosed with DPD and 48 control volunteers on measures of cognitive and affective empathy. We used self-report measures (EQ; Baron-Cohen & Wheelwright, 2004), an objective measure of cognitive empathy-the "Eyes" task (Baron-Cohen, Wheelwright, Hill, Raste, & Plumb, 2001), and a novel task tapping affective empathy, utilizing speech rate as an implicit measure of physiological arousal. We also measured participants' tendency to use mental representations that relate to the self during the affective empathy task. The DPD group showed intact performance on the cognitive empathy task. However, there was a disruption in the physiological component of affective empathy alongside a more pronounced reliance on mental representations of the self. These findings suggest affective empathy to be reliant on intact emotional experience in the observer. In addition, excessive self-focus may be detrimental to an empathic response.

Emotional memory in depersonalization disorder: a functional MRI study.

This study examines emotional memory effects in primary depersonalization disorder (DPD). A core complaint of DPD sufferers is the dulling of emotional responses, and previous work has shown that, in response to aversive stimuli, DPD patients do not show activation of brain regions involved in normal emotional processing. We hypothesized that DPD sufferers would not show the normal emotional enhancement of memory, and that they would not show activation of brain regions concerned with emotional processing during encoding and recognition of emotional verbal material. Using fMRI, 10 DPD patients were compared with an age-matched healthy control group while performing a test of emotional verbal memory, comprising one encoding and two recognition memory tasks. DPD patients showed significantly enhanced recognition for overtly emotive words, but did not show enhancement of memory for neutral words encoded in an emotive context. In addition, patients did not show activation of emotional processing areas during encoding, and exhibited no substantial difference in their neural responses to emotional and neutral material in the encoding and emotional word recognition tasks. This study provides further evidence that patients with DPD do not process emotionally salient material in the same way as healthy controls, in accordance with their subjective descriptions of reduced or absent emotional responses.

Lamotrigine as an add-on treatment for depersonalization disorder: a retrospective study of 32 cases.

OBJECTIVES: Depersonalization disorder (DPD) is a chronic condition characterized by the persistent subjective experience of unreality and detachment from the self. To date, there is no known treatment. Lamotrigine as sole agent was not found to be effective in a previous small double-blind, randomized crossover trial. However, evidence from open trials suggests that it may be beneficial as an add-on medication with antidepressants. METHODS: We report here an extended series of 32 patients with DPD in whom lamotrigine was prescribed as an augmenting medication. Most of the patients were receiving selective serotonin reuptake inhibitors. RESULTS: Fifty-six percent (n = 18) of patients had a more than or equal to 30% reduction on the Cambridge Depersonalization Scale score at follow-up. Both maximum dose of lamotrigine used and before treatment Cambridge Depersonalization Scale scores showed positive correlations with the percentage of response. CONCLUSIONS: The results of this trial suggest that a significant number of patients with DPD may respond to lamotrigine when combined with antidepressant medication. The results are sufficiently positive to prompt a larger controlled evaluation of lamotrigine as "add-on" treatment in DPD.

How metaphors influence semantic relatedness judgments: the role of the right frontal cortex.

We used event-related fMRI (ER-fMRI) to test the hypothesis that metaphors bias cognitive processing of semantic relatedness towards a search for a wider range of associations. Twelve right-handed male volunteers read a mixture of metaphoric and literal sentences, each sentence being followed by a single word, which could be semantically related or not to the preceding sentence context. We found that judging unrelated words as contextually irrelevant was associated with increased blood oxygenation level-dependent (BOLD) signal in the right ventrolateral prefrontal cortex in the metaphoric but not in the literal condition. The same region was also activated when subjects endorsed a semantic relation between words and metaphoric sentence primes but not between words and literal sentence primes. We argue that these results are consistent with the notion of semantic open-endedness, whereby figurative statements bias cognitive processing towards a search for a wider range of semantic relationships compared to literal statements, and thus lend further support to the view that coarse semantic coding occurs preferentially in the right hemisphere.

Unpacking the depersonalization syndrome: an exploratory factor analysis on the Cambridge Depersonalization Scale.

BACKGROUND: Depersonalization has long been considered a syndrome but there is poor agreement on its constituent symptoms. METHOD: In order to establish whether different symptoms of depersonalization represent the expression of a single or several underlying dimensions, an exploratory factor analysis on the Cambridge Depersonalization Scale (CDS) was carried out on 138 consecutive patients diagnosed with depersonalization disorder. RESULTS: Four well determined factors accounting for 73.3% of the variance were extracted. These were labelled 'Anomalous Body Experience'; 'Emotional Numbing'; 'Anomalous Subjective Recall' and 'Alienation from Surroundings'. CONCLUSIONS: Symptoms of depersonalization belong to distinct but related psychopathological domains.

Emotional memory: separating content and context.

It is now well established that emotion enhances episodic memory. However, it remains unclear whether the same neural processes underlie enhancement of memory for both emotional stimuli and neutral stimuli encoded in an emotive context. We designed an experiment that specifically attempted to separate these effects and that was validated on 30 participants. We then used functional magnetic resonance imaging (fMRI) to examine the neural correlates of encoding and retrieval of the two classes of stimuli in 12 healthy male volunteers. We predicted that aversive emotional context would enhance memory regardless of content and that activation of anterior cingulate would be inversely related to retrieval of aversive items. Both predictions were supported. Furthermore we demonstrated apparent asymmetrical lateralisation of activation in the hippocampal/parahippocampal complex during recognition of words from aversive sentences: more left-sided activation for neutral words from aversive contexts, and more right-sided activation for aversive content words. These findings, if applicable to the wider population, may have application in a range of psychiatric disorders where interactions between emotion and cognition are relevant.

Chronic depersonalization following illicit drug use: a controlled analysis of 40 cases.

AIMS: To examine demographic and clinical features of a group of patients reporting chronic depersonalization (DP) following illicit drug use, and to assess whether depersonalization arising in these circumstances constitutes a distinct clinical syndrome. DESIGN: Case-control comparison using self-reports, standardized questionnaires and clinical assessments in a specialized clinic. SETTING: A tertiary referral depersonalization clinic and research unit affiliated to a psychiatric hospital and research centre. PARTICIPANTS: A total of 164 individuals with chronic DP symptoms who had been in contact with the clinic. Forty of these individuals related the onset of symptoms to an episode of illicit drug use. MEASUREMENTS: A wide range of demographic and clinical variables measured using questionnaires and standardized rating scales. FINDINGS: The drug-induced DP group were significantly younger and had a preponderance of males compared to the non-drug group. Certain clinical and phenomenological differences were found between these groups, but in general the groups are strikingly similar. This is reinforced by the fact that when the drug-induced group was compared with an age and sex-matched subset of the non-drug group, differences between groups largely disappeared. CONCLUSIONS: Drug-induced DP does not appear to represent a distinct clinical syndrome. The neurocognitive mechanisms of the genesis and maintenance of DP are likely to be similar across clinical groups, regardless of precipitants.

Depersonalisation disorder: clinical features of 204 cases.

BACKGROUND: Depersonalisation disorder is a poorly understood and underresearched syndrome. AIMS: To carry out a large and comprehensive clinical and psychopathological survey of a series of patients who made contact with a research clinic. METHOD: A total of 204 consecutive eligible referrals were included: 124 had a full psychiatric examination using items of the Present State Examination to define depersonalisation/derealisation and 80 had either a telephone interview (n=22) or filled out a number of self-report questionnaires. Cases assessed were diagnosed according to DSM-IV criteria. RESULTS: The mean age of onset was 22.8 years; early onset was associated with greater severity. There was a slight male preponderance. The disorder tended to be chronic and persistent. Seventy-one per cent met DSM-IV criteria for primary depersonalisation disorder. Depersonalisation symptom scores correlated with both anxiety and depression and a past history of these disorders was commonly reported. 'Dissociative amnesia' was not prominent. CONCLUSIONS: Depersonalisation disorder is a recognisable clinical entity but appears to have significant comorbidity with anxiety and depression. Research into its aetiology and treatment is warranted.